In the face of increasingly serious environmental pollution,the health of human lung tissues is also facing serious threats.Mogroside IIE(M2E)is the main metabolite of sweetening agents mogrosides from the anti-tussiv...In the face of increasingly serious environmental pollution,the health of human lung tissues is also facing serious threats.Mogroside IIE(M2E)is the main metabolite of sweetening agents mogrosides from the anti-tussive Chinese herbal Siraitia grosvenori.The study elucidated the anti-inflammatory action and molecular mechanism of M2E against acute lung injury(ALI).A lipopolysaccharide(LPS)-induced ALI model was established in mice and MH-S cells were employed to explore the protective mechanism of M2E through the western blotting,co-immunoprecipitation,and quantitative real time-PCR analysis.The results indicated that M2E alleviated LPS-induced lung injury through restraining the activation of secreted phospholipase A2 type IIA(Pla2g2a)-epidermal growth factor receptor(EGFR).The interaction of Pla2g2a and EGFR was identified by co-immunoprecipitation.In addition,M2E protected ALI induced with LPS against inflammatory and damage which were significantly dependent upon the downregulation of AKT and m TOR via the inhibition of Pla2g2a-EGFR.Pla2g2a may represent a potential target for M2E in the improvement of LPS-induced lung injury,which may represent a promising strategy to treat ALI.展开更多
Objective To explore the relationship between ulcerative colitis(UC) and lung injuries by assessing their clinical manifestations and characteristics. Methods From July 2009 to April 2012, 91 UC patients presenting to...Objective To explore the relationship between ulcerative colitis(UC) and lung injuries by assessing their clinical manifestations and characteristics. Methods From July 2009 to April 2012, 91 UC patients presenting to Longhua Hospital who met the established inclusion and exclusion criteria were enrolled in this retrospective study. According to the scores of disease activity index, the patients were divided into the mild, moderate, and severe groups. Meanwhile, the records of pulmonary symptoms, chest X-ray image, and pulmonary function were reviewed. Results Sixty-eight(74.7%) patients had at least 1 pulmonary symptom, such as cough(38.5%), shortness of breath(27.5%), and expectoration(17.6%). And 77(84.6%) had at least 1 ventilation abnormality. Vital capacity value was significantly lower in the severe group than that in the mild group(91.82%±10.38% vs. 98.92%±12.12%, P<0.05). Conclusions Lung injury is a common extraintestinal complication of UC. According to the theory in Traditional Chinese Medicine that the lung and large intestine are related, both the lungs and large intestine should be treated simultaneously.展开更多
BACKGROUND: Acute lung injury(ALI) is a common and serious complication of severe acute pancreatitis(SAP). The study aimed to investigate the protective effect and mechanism of phosphatidylinositol-3 kinase(PI3K) inhi...BACKGROUND: Acute lung injury(ALI) is a common and serious complication of severe acute pancreatitis(SAP). The study aimed to investigate the protective effect and mechanism of phosphatidylinositol-3 kinase(PI3K) inhibitor Wortmannin in SAP associated with ALI.METHODS: Ninety rats were randomly divided into three groups: sham operation(SO) group(n=30), SAP group(n=30), and SAP+Wortmannin(SAP+W) group(n=30). SAP model was induced by retrograde injection of 4% sodium taurocholate into the biliopancreatic duct of rats. The rate of lung water content, myeloperoxidase(MPO), matrix metalloproteinase 9(MMP-9), protein kinase B(PKB), abdphosphorylation of protein kinase B(P-PKB) activity in the lung tissue were evaluated.RESULTS: In the SAP group, the p-PKB expression in the lung tissue began to rise at 3 hours after modeling, and peaked at 12 hours(P<0.05); the rate of lung water content, MPO and TNF-α activity were also gradually increased, and the degree of lung lesion gradually increased(P<0.05). In the SAP+Wortmannin group, the p-PKB expression in the lung tissue began to rise at 3 hours after modeling, and peaked at 12 hours; it was higher than that in the SO group(P<0.05), but significantly lower than that in the SAP group(P<0.05). The rest indicators in the SAP+Wortmannin group were also significantly decreased as compared with the SAP group(P<0.05).CONCLUSIONS: The expression of phosphatidylinositol-3 kinase/protein kinase B was elevated in severe pancreatitis rats with lung injury. This suggested that PI3 K signal transduction pathway is involved in the control and release of proinfl ammatory cytokines TNF-α, which may play an important role in the pathogenesis of severe acute pancreatitis associated with lung injury. This finding indicated that Wortmannin can block the PI3 K signal transduction pathway, and inhibit the release of infl ammatory factor TNF-α.展开更多
BACKGROUND:Platelet endothelial cell adhesion molecule-1(PECAM-1),also known as CD31,is mainly distributed in vascular endothelial cells.Studies have shown that PECAM-1 is a very significant indicator of angiogenesis,...BACKGROUND:Platelet endothelial cell adhesion molecule-1(PECAM-1),also known as CD31,is mainly distributed in vascular endothelial cells.Studies have shown that PECAM-1 is a very significant indicator of angiogenesis,and has been used as an indicator for vascular endothelial cells.The present study aimed to explore the relationship between the expression of PECAM-1 and the degree of acute lung injury(ALI) and fibrosis in paraquat(PQ) induced lung injury in rabbits.METHODS:Thirty-six adult New Zealand rabbits were randomly divided into three groups(12rabbits in each group) according to PQ dosage:8 mg/kg(group A),16 mg/kg(group B),and 32 mg/kg(group C).After PQ infusion,the rabbits were monitored for 7 days and then euthanized.The lungs were removed for histological evaluation.Masson staining was used to determine the degree of lung fibrosis(LF),and semi-quantitative immune-histochemistry analysis to determine the expression of PECAM-1.Pearson's product-moment correlation analysis was performed to evaluate the relationship between the expression of PECAM-1 and the extent of lung injuries expressed by ALI score and degree of LF.RESULTS:Rabbits in the three groups showed apparent poisoning.The rabbits survived longer in group A than in groups B and C(6.47±0.99 days vs.6.09±1.04 days vs.4.77±2.04 days)(P<0.05).ALI score was lower in group A than in groups B and C(8.33±1.03 vs.9.83±1.17 vs.11.50±1.38)(P<0.05),and there was statistically significant difference between group B and group C(P=0.03).LF was slighter in group A than in groups B and C(31.09%±2.05%vs.34.37%±1.62%vs.36.54%±0.44%)(P<0.05),and there was statistically significant difference between group B and group C(P=0.026).The PEACAM-1 expression was higher in group A than in groups B and C(20.31%±0.70%vs.19.34%±0.68%vs.18.37%±0.46%)(P<0.05),and there was statistically significant difference between group B and group C(P=0.017).Pearson's correlation analysis showed that the expression of PECAM-1 was negatively correlated to both ALI score(Coe=-0.732,P=0.001)and degree of LF(Coe=-0.779,P<0.001).CONCLUSIONS:The PECAM-1 expression significantly decreases in New Zealand rabbits after PQ poisoning,and the decrease is dose-dependent.The PECAM-1 expression is negatively correlated with ALI score and LF,showing a significant role in the development of lung injuries induced by PQ.展开更多
Acute lung injury （ALl） or acute respiratory distress syndrome （ARDS） can be associated with various disorders. Recent investigation has involved clinical studies in collaboration with clinical investigators and p...Acute lung injury （ALl） or acute respiratory distress syndrome （ARDS） can be associated with various disorders. Recent investigation has involved clinical studies in collaboration with clinical investigators and pathologists on the pathogenetic mechanisms of ALl or ARDS caused by various disorders. This literature review includes a brief historical retrospective of ALI/ARDS, the neurogenic pulmonary edema due to head injury, the long-term experimental studies and clinical investigations from our laboratory, the detrimental role of NO, the risk factors, and the possible pathogenetic mechanisms as well as therapeutic regimen for ALI/ARDS.展开更多
BACKGROUND： Mechanical ventilation is a double-edged sword to acute respiratory distress syndrome （ARDS） including lung injury, and systemic inflammatory response high tidal volumes are thought to increase mortalit...BACKGROUND： Mechanical ventilation is a double-edged sword to acute respiratory distress syndrome （ARDS） including lung injury, and systemic inflammatory response high tidal volumes are thought to increase mortality. The objective of this study is to evaluate the effects of dynamic ventilatory factors on ventilator induced lung injury in a dog model of ARDS induced by hydrochloric acid instillation under volume controlled ventilation and to investigate the relationship between the dynamic factors and ventilator-induced lung injuries （VILI） and to explore its potential mechanisms.METHODS： Thirty-six healthy dogs were randomly divided into a control group and an experimental group. Subjects in the experimental group were then further divided into four groups by different inspiratory stages of flow. Two mL of alveolar fluid was aspirated for detection of IL-8 and TNF-α. Lung tissue specimens were also extracted for total RNA, IL-8 by western blot and observed under an electronic microscope.RESULTS： IL-8 protein expression was significantly higher in group B than in groups A and D. Although the IL-8 protein expression was decreased in group C compared with group B, the difference was not statistically significant. The TNF-a ray degree of group B was significantly higher than that in the other groups （P〈0.01）, especially in group C （P〉0.05）. The alveolar volume of subjects in group B was significantly smaller, and cavity infiltration and cell autolysis were marked with a significant thicker alveolar septa, disorder of interval structures, and blurring of collagenous and elastic fiber structures. A large number of necrotic debris tissue was observed in group B.CONCLUSION： Mechanical ventilation with a large tidal volume, a high inspiratory flow and a high ventilation frequency can cause significant damage to lung tissue structure. It can significantly increase the expression of TNF-α and IL-8 as well as their mRNA expression. Furthermore, the results of our study showed that small tidal ventilation significantly reduces the release of proinflammatory media. This finding suggests that greater deterioration in lung injury during ARDS is associated with high inspiratory flow and high ventilation rate.展开更多
Objective. To approach the relation and the possible mechanism between the expression of intercellular adhesion molecule (ICAM1) mRNA and acute lung injury (ALI) and the mechanisms of rhubarb in the prevention and tre...Objective. To approach the relation and the possible mechanism between the expression of intercellular adhesion molecule (ICAM1) mRNA and acute lung injury (ALI) and the mechanisms of rhubarb in the prevention and treatment of the lung injury. Methods. Lipopolysaccharide (LPS) was injected into the sublingual vein of male Wistar rats to perform ALI animal model. The rats were divided into 4 groups: LPS group, control group, rhubarb group and dexamethasone group. Macroscopic and histopathological examinations were performed and biological markers were measured for the lung specimens. The markers included lung wet/dry weight, the rate of neutrophils and protein content in the pulmonary alveolar lavage fluid, pulmonary vascular permeability and pulmonary alveolar permeability index. Molecular hybridization method was used to determine the expression of ICAM1 mRNA. Results. In the lung tissues, the ICAM1 mRNA expression was increased in the endothelial cells of pulmonary veins and capillaries, rhubarb and dexamethasone had the action of decreasing the expression. The light reflex value in the gray scale scanning showed that in the comparison between the LPS and the control group, the gray scale value of the lung tissues in ALI was significantly increased, thus the light reflex value was markedly decreased (P<001), demonstrating the expression of ICAM1 mRNA was increased. In comparison with the LPS group, dexamethasone and rhubarb could decrease the gray scale value of the lung tissue significantly, thus the light reflex value was elevated (P<001, P<005); the corresponding pathologic changes of lung tissues and the biological markers of the lung injury were significantly decreased or ameliorated. Conclusions. The increase of the expression of ICAM1 mRNA in the lung tissues of ALI plays the roles in ALI. The application of rhubarb and dexamethasone can decrease the expression and ameliorate the lung damage; its mechanism is possibly via the inhibition of ICAM1 mRNA expression.展开更多
BACKGROUND: The present study was undertaken to examine the regulatory effect of hydrogen sulfide(H2S) on endoplasmic reticulum stress in alveolar epithelial cells of rats with acute lung injury(ALI) induced by oleic ...BACKGROUND: The present study was undertaken to examine the regulatory effect of hydrogen sulfide(H2S) on endoplasmic reticulum stress in alveolar epithelial cells of rats with acute lung injury(ALI) induced by oleic acid(OA).METHODS: Seventy-two male Sprague Dawley(SD) rats were divided into control group, oleic acid-induced ALI group(OA group), oleic acid-induced ALI with sodium hydrosulfide(Na HS) pretreatment group(OA+Na HS group), and sodium hydrosulfide treatment group(Na HS group). Rats of each group were further subdivided into 3 subgroups. Index of quantitative assessment of histological lung injury(IQA), wet/dry weight ratio(W/D) and H2 S level of lung tissues were measured. The expressions of endoplasmic reticulum stress markers including glucose-regulated protein 78(GRP78) and α-subunit of eukaryotic translation initiation factor-2(el F2α) in lung tissues were measured by immunohistochemical staining and Western blotting.RESULTS: The IQA score and W/D ratio of lung tissues at the three time points significantly increased in rats injected with OA, but significantly decreased in other rats injected with OA and Na HS. The level of H2 S in lung tissue at the three time points significantly decreased in rats injected with OA, but significantly increased in other rats injected with both OA and Na HS. GRP78 and el F2α decreased in rats injected with OA, but increased in other rats injected with both OA and Na HS, especially at 4-hour and 6-hour time points.CONCLUSION: The results suggested that H2 S could promote alveolar epithelial cell endoplasmic reticulum stress in rats with ALI.展开更多
Objective To explore whether the amount of lipocalin-2 in the biofluid could reflect the onset of sepsis-induced acute lung injury(ALI) in mice. Methods Lipopolysaccharide(LPS, 10 mg/kg) injection or cecal ligation an...Objective To explore whether the amount of lipocalin-2 in the biofluid could reflect the onset of sepsis-induced acute lung injury(ALI) in mice. Methods Lipopolysaccharide(LPS, 10 mg/kg) injection or cecal ligation and puncture(CLP) was performed to induce severe sepsis and ALI in C57 BL/6 male mice randomly divided into 5 groups(n=10 in each group): group A(intraperitoneal LPS injection), group B(intravenous LPS injection via tail vein), group C(CLP with 25% of the cecum ligated), group D(CLP with 75% of the cecum ligated), and the control group(6 sham-operation controls plus 4 saline controls). All the mice received volume resuscitation. Measurements of pulmonary morphological and functional alterations were used to identify the presence of experimental ALI. The expressions of lipocalin-2 and interleukin(IL)-6 in serum, bronchoalveolar lavage fluid(BALF), and lung tissue were quantified at both protein and mRNA levels. The overall abilities of lipocalin-2 and IL-6 tests to diagnose sepsis-induced ALI were evaluated by generating receiver operator characteristic curves(ROC) and computing area under curve(AUC). Results In both group B and group D, most of the "main features" of experimental ALI were reproduced in mice, while group A and group C showed septic syndrome without definite evidence for the presence of ALI. Compared with septic mice without ALI(group A+group C), lipocalin-2 protein expression in septic mice with ALI(group B+group D) was significantly up-regulated in BALF(P<0.01) and in serum(P<0.01), and mRNA expression boosted in lung tissues(all P<0.05). Lipocalin-2 tests performed better than IL-6 tests in recognizing sepsis-induced ALI cases, evidenced by the larger AUC of the former(BALF tests, 0.8800 versus 0.6625; serum tests, 0.8500 versus 0.7000). Using a dual cutoff system to diagnose sepsis-induced ALI, BALF lipocalin-2 test exhibited the highest positive likelihood ratio(13.000) and the lowest negative likelihood ratio(0.077) among the tests of lipocalin-2 and IL-6 in blood and BALF. A statistically significant correlation was found between lipocalin-2 concentration in BALF and that in serum(Spearman r=0.8803,P<0.0001). Conclusions Lipocalin-2 expression is significantly up-regulated in septic ALI mice compared with those without ALI. Lipocalin-2 tests with a dual cutoff system could be an effective tool in distinguishing experimental ALI cases.展开更多
BACKGROUND： This study was undertaken to determine the effect of mesenchymal stem cells （MSCs） engraftment on vascular endothelial cell growth factor （VEGF） in lung tissue, plasma and extravascular lung water at...BACKGROUND： This study was undertaken to determine the effect of mesenchymal stem cells （MSCs） engraftment on vascular endothelial cell growth factor （VEGF） in lung tissue, plasma and extravascular lung water at early stage of smoke inhalation injury.METHODS： A rabbit smoke inhalation injury model was established using a home-made smoke inhalation injury generator, and rabbits were divided into two groups randomly： a control group （S group, n=32） and a MSCs treatment group （M group, n=32）. 10 ml PBS was injected via the ear marginal vein immediately at injury into the S group. Third generation MSCs with a concentration of 1×107/10 ml PBS were injected via the ear marginal vein immediately at injury into the M group. VEGF in peripheral blood and lung tissue were measured at 0 （baseline）, 2, 4 and 6 hours after injection respectively and analyzed. The right lungs of rabbits were taken to measure lung water mass fraction.RESULTS： In the lung tissue, VEGF decreased gradually in the S group （P〈0.05） and signi？ cantly decreased in the M group （P〈0.05）, but it increased more signi？ cantly than the values at the corresponding time points （P〈0.05）. In peripheral blood, VEGF increased gradually in the S group （P〈0.05） and markedly increased in the M group （P〈0.05）, but it decreased more signi？ cantly than the values at corresponding time points （P〈0.05）.CONCLUSION： MSCs engraftment to smoke inhalation injury could increase VEGF in lung tissue, decrease VEGF in plasma and reduce extravascular lung water, indicating its protective effect on smoke inhalation injury.展开更多
Objective: To explore the effects of altitude hypoxia on septic pulmonary injury (3080 m above sea level). Methods : A model of pyosepticemia was established by cecal ligation and puncture. Thromboxane A2 (TXA2),prost...Objective: To explore the effects of altitude hypoxia on septic pulmonary injury (3080 m above sea level). Methods : A model of pyosepticemia was established by cecal ligation and puncture. Thromboxane A2 (TXA2),prostacyclin (PGI2) of the venous plasma and leucine-enkephalins (L-ENK) in the arterial walls were measured using radioiizimunoassay in 31 rabbits. Mouse morrality was observed. Results: 24 h mouse accumulative mortality (97. 1% )was greater than that of control (35%). TXB2 content was 4 times as much as in control group and 6-keto-PGF1α level was elevated too. These changes of arachidonic metabolism could be blorked by indomethacin. The contents of LENK in arterial walls of puhiionary, mesenteric and renal arteries dropped significantly in comparison with control group (P<0. 01 ). The albumin content in the bronchoalveolar lavage fluid rase significantly in comparison with control group (P<0. 01 ). Conclusion : The results demonstrate that the metabolites of cyclcoxygenase are not the major mediator of puhiionary permeability in the experiment. The alteration of TXA2 and L-ENK contents may be one of the mechanisms, by which the puhiionary artery pressure and pulmonary vascular resistance are increased during sepsis.展开更多
Background:Aeromedical evacuation of patients with burn trauma is an important transport method in times of peace and war,during which patients are exposed to prolonged periods of hypobaric hypoxia;however,the effects...Background:Aeromedical evacuation of patients with burn trauma is an important transport method in times of peace and war,during which patients are exposed to prolonged periods of hypobaric hypoxia;however,the effects of such exposure on burn injuries,particularly on burn-induced lung injuries,are largely unexplored.This study aimed to determine the effects of hypobaric hypoxia on burn-induced lung injuries and to investigate the underlying mechanism using a rat burn model.Methods:A total of 40 male Wistar rats were randomly divided into four groups(10 in each group):sham burn(SB)group,burn in normoxia condition(BN)group,burn in hypoxia condition(BH)group,and burn in hypoxia condition with treatment intervention(BHD)group.Rats with 30%total body surface area burns were exposed to hypobaric hypoxia(2000 m altitude simulation)or normoxia conditions for 4 h.Deoxyribonuclease I(DNase I)was administered systemically as a treatment intervention.Systemic inflammatory mediator and mitochondrial deoxyribonucleic acid(mtDNA)levels were determined.A histopathological evaluation was performed and the acute lung injury(ALI)score was determined.Malonaldehyde(MDA)content,myeloperoxidase(MPO)activity,and the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3(NLRP3)inflammasome level were determined in lung tissues.Data among groups were compared using analysis of variance followed by Tukey’s test post hoc analysis.Results:Burns resulted in a remarkably higher level of systemic inflammatory cytokines and mtDNA release,which was further heightened by hypobaric hypoxia exposure(P<0.01).Moreover,hypobaric hypoxia exposure gave rise to increased NLRP3 inflammasome expression,MDA content,and MPO activity in the lung(P<0.05 or P<0.01).Burn-induced lung injuries were exacerbated,as shown by the histopathological evaluation and ALI score(P<0.01).Administration of DNase I markedly reduced mtDNA release and systemic inflammatory cytokine production.Furthermore,the NLRP3 inflammasome level in lung tissues was decreased and burn-induced lung injury was ameliorated(P<0.01).Conclusions:Our results suggested that simulated aeromedical evacuation further increased burn-induced mtDNA release and exacerbated burn-induced inflammation and lung injury.DNase I reduced the release of mtDNA,limited mtDNA-induced systemic inflammation,and ameliorated burn-induced ALI.The intervening mtDNA level is thus a potential target to protect from burn-induced lung injury during aeromedical conditions and provides safer air evacuations for severely burned patients.展开更多
Low tidal volume mechanical ventilation is difficult to correct hypoxemia, and prolonged inhalation of pure oxygen can lead to oxygen poisoning. We suggest that continuous tracheal gas insufflation （TGI） during prot...Low tidal volume mechanical ventilation is difficult to correct hypoxemia, and prolonged inhalation of pure oxygen can lead to oxygen poisoning. We suggest that continuous tracheal gas insufflation （TGI） during protective mechanical ventilation could improve cardiopulmonary function in acute lung injury. Totally 12 healthy juvenile piglets were anesthetized and mechanically ventilated at PEEP of 2 cmH2O with a peak inspiratory pressure of 10 cmH2O. The piglets were challenged with lipopolysaccharide and randomly assigned into two groups （n=6 each group）： mechanical ventilation （MV） alone and TGI with continuous airway flow 2 I/min. FIO2 was set at 0.4 to avoid oxygen toxicity and continuously monitored with an oxygen analyzer. Tidal volume, ventilation efficacy index and mean airway resistant pressure were significantly improved in the TGI group （P〈0.01 or P〈0.05）. At 4 hours post ALl, pH decreased to below 7.20 in the MV group, and improved in the TGI group （P〈0.01）. Similarly, PaCO2 was stable and was significantly lower in the TGI group than in the MV group （P〈0.01）. PaO2 and PaO2/FIO2 increased also in the TGI group （P〈0.05）. There was no significant difference in heart rate, respiratory rate, mean artery pressure, central venous pressure, dynamic lung compliance and mean resistance of airway between the two groups. Lung histological examination showed reduced inflammation, reduced intra- alveolar and interstitial patchy hemorrhage, and homogenously expanded lungs in the TGI group. Continuous TGI during MV can significantly improve gas exchange and ventilation efficacy and may provide a better treatment for acute lung injury.展开更多
Objective To determine whether the onset of acute lung injury （ALl） induces the up-regulation of pentraxin 3 （PTX3） expression in mice and whether PTX3 concentration in the biofluid can help recognizing sepsis-ind...Objective To determine whether the onset of acute lung injury （ALl） induces the up-regulation of pentraxin 3 （PTX3） expression in mice and whether PTX3 concentration in the biofluid can help recognizing sepsis-induced ALI. Methods Wild-type C57BL/6 mice （12-14 weeks old） were randomly divided into 3 groups. Mice in the group 1 （n=12） and group 2 （n=12） were instilled with lipopolysaccharide via intratracheal or intraperitoneal routes, respectively. Mice in the group 3 （n=8） were taken as blank controls. Pulmonary morphological and functional alterations were measured to determine the presence of experimental ALl. PTX3 expression in the lung was quantified at both protein and mRNA levels. PTX3 protein concentration in blood and bronchoalveolar lavage fluid was measured to evaluate its ability to diagnose sepsis-induced ALI by computing area under receiver operator characteristic curve （AUROCC）. Results ALl was commonly confirmed in the group 1 but never in the other groups. PTX3 expression was up-regulated indiscriminately among lipopolysaccharide-challenged mice. PTX3 protein concentration in the biofluid was unable to diagnose sepsis-induced ALl evidenced by its small AUROCC. PTX3 concentration in bronchoalveolar lavage fluid did not correlate with that in serum. Conclusions Lipopolysaccharide challenges induced PTX3 expression in mice regardless of the presence ofALI. PTX3 may act as an indicator of inflammatory response instead of organ injury per se.展开更多
In cases of severe sepsis and septic shock, a series of pathophysiological changes lead to multiple organ dysfunction syndrome.This study aimed to investigate the expression of glucocorticoid receptor mRNA in the rat ...In cases of severe sepsis and septic shock, a series of pathophysiological changes lead to multiple organ dysfunction syndrome.This study aimed to investigate the expression of glucocorticoid receptor mRNA in the rat lung following endotoxin （LPS） induced shock. Totally 56 SD rats were randomly divided into 4 groups： LPS shock group （n=16）, LPS＋vasoactive intestinal peptide group（VIP） group, （n=16）, LPS＋VIP＋ glucocorticoid （GC） group, （n=16）,and control group （n=8）. LPS shock was induced by intravenous injection of LPS （10 mg/kg） in rats. Within 15 minutes after LPS injection, rats in the treatment groups received VIP （5 nmol/kg） or VIP and methylprednisolone （3 mg/kg）. The control group was given normal saline instead of LPS. The rats of the four groups were sacrificed at 6 hours,24 hours after injection respectively, and the lung tissues were collected. Pathological changes of the lungs were examined by light microscopy and electron microscopy. GRmRNA expression in the lung tissues was evaluated by RT-PCR. In the LPS shock group, lung histopathology demonstrated destruction of the alveolar space,widening of the inter-alveolar space, inflammatory cell infiltration and interstitial edema. However,pathological changes in the LPS＋ VIP group and LPS＋ VIP＋GC group were milder than those in the LPS shock group. Six hours after LPS injection, GR mRNA expression was down-regulated in the LPS group （0.72± 0.24） and LPS＋ VIP group （0.88±0.27） （P〈0.05） as compared with the control group （1.17±0.22）. The LPS shock group showed a more significant down-regualtion than the LPS＋VIP group, but the difference was not statistically significant （P〉0.05）. In contrast, GRmRNA expression in the LPS＋ VIP＋GC group was significantly up-regulated at 6 hours and further at 24 hours （1.45±0.32 and 1.91±0.46 respectively） （P〈0.05）. GrmRNA expression decreased in LPS induced lung injury in rats. Combined treatment with VIP and GC mitigated lung injury ang inflammation. The mechanism may be related to up-regulation of GR mRNA expression.展开更多
BACKGROUND： This study aimed to observe the effect of recruitment maneuver （RM） and post-RM ventilation at different tidal volume on lung vascular diastole endothelial function in rats with acute lung injury （ALI...BACKGROUND： This study aimed to observe the effect of recruitment maneuver （RM） and post-RM ventilation at different tidal volume on lung vascular diastole endothelial function in rats with acute lung injury （ALI）.METHODS： A ALl rat model was produced by intravenous infusion of lipopolysaccharide （6 mg/ kg）. Twenty-five rats were randomly divided into five groups： control group （n=5）, ALl group （n=5）, low tidal volume group （LV group, VT 6 mL/kg, n=5）, sustained inflation （SI） with low tidal volume group （SI＋LV group, VT 6 mL/kg, n=5）, and SI with moderate tidal volume group （SI＋MV group, VT 12 mL/ kg, n=5）. RM was performed with SI, airway pressure 30 cmH2O for 30 seconds, and positive end- expiratory pressure （PEEP） was set to 5 cmH2O. Lung tissue was taken after 5 hours of mechanical ventilation. Mean arterial blood pressure （MAP） was monitored during the experiment. Endothelin-1 （ET-1）, endothelial nitricoxide synthase （eNOS）, Ach-induced endothelium-dependent relaxation response of isolated pulmonary artery rings were determined at 5 hours. RESULTS：LPS increased ET-1 level, decreased the expression of eNOS in lung tissue, impaired the Ach-induced endothelium-dependent relaxation response in the pulmonary artery, without obvious effect on systemic hemodynamics. SI＋LV significantly reduced LPS-induced elevation of ET-1 level, increased the expression of eNOS, significantly improved endothelial dysfunction, and improved the dysfunction of endothelium-dependent relaxation in the pulmonary artery. CONCLUSIONS：RM with a high or low tidal volume ventilation could improve the lung vascular endothelial function of rats with acute lung injury, and RM with low tidal volume ventilation could lower significantly the injury of lung vascular endothelial diastole function in rats with acute lung injury.展开更多
BACKGROUND： Myeloid cell （TREM-1） is an important mediator of the signal transduction pathway in inflammatory response. In this study, a mouse model of acute lung injury （ALl） by intraperitoneal injection of lipo...BACKGROUND： Myeloid cell （TREM-1） is an important mediator of the signal transduction pathway in inflammatory response. In this study, a mouse model of acute lung injury （ALl） by intraperitoneal injection of lipopolysaccharide （LPS） was established to observe the expression pattern of TREM-1 in lung tissue and the role of TREM-1 in pulmonary inflammatory response to ALl.METHODS： Thirty BALB/C mice were randomly divided into a normal control group （n=6） and an ALl group （n=24）. The model of ALl was made by intraperitonal injection of LPS in dose of 10 mg/ kg. Specimens from peripheral blood and lung tissue were collected 6, 12, 24 and 48 hours after LPS injection. RT-PCR was used to detect TREM-1 mRNA, and ELISA was employed for detection of TREM-1 protein and TNF-a protein, and HE staining was performed for the pathological Smith lung scoring under a light microscope.RESULTS： The expressions of TREM-1 mRNAin lung tissue and blood of the ALl group 6, 12, 24, and 48 hours after injection of LPS were higher than those in the control group. The levels of TREM- 1 protein and the levels of TNF-a protein in lung tissue of the ALl group 6, 12, 24, and 48 hours after LPS injection were higher than those of the control group; the level of TREM-1 protein peaked 12 hours after LPS injection, but it was not significantly correlated with the expression of TREM-1 mRNA （P=0.14）; the TNF-a concentration was positively correlated with TREM-1 levels in lung tissue and with Smith pathological score （r=0.795, P=0.001 ：r=0.499, P=0.034）, but not with the expression of TREM-1 mRNA （P=0.176）.CONCLUSION： The expression of TREM-1 mRNA in lung tissue of mice with ALl is elevated, and the expression of TREM-1 mRNA is related to the level of TNF-a and the severity of inflammatory response to ALl. The expressions of the TREM-1 gene are not consistent with the levels of TREM-1 protein, suggesting a new functional protein involved in immune regulation.展开更多
We studied the functional changes of pulmonary surfactant （PS） in acutelung injury models produced by endotoxin injection (E.coli O<sub>55</sub>B<sub>5</sub>) in rats.The sur-face properties ...We studied the functional changes of pulmonary surfactant （PS） in acutelung injury models produced by endotoxin injection (E.coli O<sub>55</sub>B<sub>5</sub>) in rats.The sur-face properties of the lung lavage liquid and the total phospholipids （TPL） ex-tracted from it were assessed on a modified Wilhelmy film balance.γ-A isothermof the lavage liquid revealed an increase in minimum surface tension and a de-crease in hysteresis area,recruitment index and stability index,whereas that ofTPL extracted from it did not show any change except for hysteresis area.Thesurface activity correlates positively with the TPL content but negatively with thetotal protein content in the lavage liquid.The findings indicated that there was adysfunction of PS in rats with the lung injury induced by endotoxin,suggestingthat the function deficiency of PS might be caused by decreased phospholipidsand increased proteins in the alveoli.展开更多
We tried to clarify the role of oxygen radicals released from granulocytes stimulated byphorbol myristate acetate(PMA) in rat acute lung injury. It was found that DNA strand-breakdamage(DSBD) in peripheral white blood...We tried to clarify the role of oxygen radicals released from granulocytes stimulated byphorbol myristate acetate(PMA) in rat acute lung injury. It was found that DNA strand-breakdamage(DSBD) in peripheral white blood cells (WBC) was significantly increased 40 min after injec-tion of PMA. DSBD in lung tissue of rats treated with PMA was also markedly increased comparedwith the controls. The PMA-treated rats showed significantly higher lipid-peroxide (LPO) level inplasma and lung tissue hemogenate than the controls did. These results suggest that determination ofDSBD, a simple and sensitive indicator for oxygen radical damaging, might be useful in thediagnosis of adult respiratory distress syndrome (ARDS), when it is used together with themeasurement of plasma LPO.展开更多
Changes of pulmonary α1-and βadrenergic receptors (α1- ARs and β-ARs) after endotoxin-induced lung injury were dynamically observed with radioligand binding assay and the pulmonary rnicrovascular permeability and ...Changes of pulmonary α1-and βadrenergic receptors (α1- ARs and β-ARs) after endotoxin-induced lung injury were dynamically observed with radioligand binding assay and the pulmonary rnicrovascular permeability and histopathology were also studied in rats to investigate the relationship between changes of pu1monary ARs and acute lung injury. It was found that the contents of both α1-ARs and β-ARs were significantly decreased after endotoxin-induced acute lung injury. On the basis of these findings, the authors inferred that the down regulation of β-ARs might be one of the factors to increase pulmonary microvascular permeability and that of α1-ARs seems to be a protective reaction. This inference might serve as the theoretical basis to treat pulmonary edema with α1-antagonists and β-agonists clinically.展开更多
基金the National Natural Science Foundation(81773982,82003937)Youth Academic leaders of the Qinglan Project in Jiangsu province for financial support。
文摘In the face of increasingly serious environmental pollution,the health of human lung tissues is also facing serious threats.Mogroside IIE(M2E)is the main metabolite of sweetening agents mogrosides from the anti-tussive Chinese herbal Siraitia grosvenori.The study elucidated the anti-inflammatory action and molecular mechanism of M2E against acute lung injury(ALI).A lipopolysaccharide(LPS)-induced ALI model was established in mice and MH-S cells were employed to explore the protective mechanism of M2E through the western blotting,co-immunoprecipitation,and quantitative real time-PCR analysis.The results indicated that M2E alleviated LPS-induced lung injury through restraining the activation of secreted phospholipase A2 type IIA(Pla2g2a)-epidermal growth factor receptor(EGFR).The interaction of Pla2g2a and EGFR was identified by co-immunoprecipitation.In addition,M2E protected ALI induced with LPS against inflammatory and damage which were significantly dependent upon the downregulation of AKT and m TOR via the inhibition of Pla2g2a-EGFR.Pla2g2a may represent a potential target for M2E in the improvement of LPS-induced lung injury,which may represent a promising strategy to treat ALI.
基金Supported by the New Project of Traditional Chinese Medicine of Shanghai Health and Family Planning Commission for the next three years(LH02.28.006)
文摘Objective To explore the relationship between ulcerative colitis(UC) and lung injuries by assessing their clinical manifestations and characteristics. Methods From July 2009 to April 2012, 91 UC patients presenting to Longhua Hospital who met the established inclusion and exclusion criteria were enrolled in this retrospective study. According to the scores of disease activity index, the patients were divided into the mild, moderate, and severe groups. Meanwhile, the records of pulmonary symptoms, chest X-ray image, and pulmonary function were reviewed. Results Sixty-eight(74.7%) patients had at least 1 pulmonary symptom, such as cough(38.5%), shortness of breath(27.5%), and expectoration(17.6%). And 77(84.6%) had at least 1 ventilation abnormality. Vital capacity value was significantly lower in the severe group than that in the mild group(91.82%±10.38% vs. 98.92%±12.12%, P<0.05). Conclusions Lung injury is a common extraintestinal complication of UC. According to the theory in Traditional Chinese Medicine that the lung and large intestine are related, both the lungs and large intestine should be treated simultaneously.
文摘BACKGROUND: Acute lung injury(ALI) is a common and serious complication of severe acute pancreatitis(SAP). The study aimed to investigate the protective effect and mechanism of phosphatidylinositol-3 kinase(PI3K) inhibitor Wortmannin in SAP associated with ALI.METHODS: Ninety rats were randomly divided into three groups: sham operation(SO) group(n=30), SAP group(n=30), and SAP+Wortmannin(SAP+W) group(n=30). SAP model was induced by retrograde injection of 4% sodium taurocholate into the biliopancreatic duct of rats. The rate of lung water content, myeloperoxidase(MPO), matrix metalloproteinase 9(MMP-9), protein kinase B(PKB), abdphosphorylation of protein kinase B(P-PKB) activity in the lung tissue were evaluated.RESULTS: In the SAP group, the p-PKB expression in the lung tissue began to rise at 3 hours after modeling, and peaked at 12 hours(P<0.05); the rate of lung water content, MPO and TNF-α activity were also gradually increased, and the degree of lung lesion gradually increased(P<0.05). In the SAP+Wortmannin group, the p-PKB expression in the lung tissue began to rise at 3 hours after modeling, and peaked at 12 hours; it was higher than that in the SO group(P<0.05), but significantly lower than that in the SAP group(P<0.05). The rest indicators in the SAP+Wortmannin group were also significantly decreased as compared with the SAP group(P<0.05).CONCLUSIONS: The expression of phosphatidylinositol-3 kinase/protein kinase B was elevated in severe pancreatitis rats with lung injury. This suggested that PI3 K signal transduction pathway is involved in the control and release of proinfl ammatory cytokines TNF-α, which may play an important role in the pathogenesis of severe acute pancreatitis associated with lung injury. This finding indicated that Wortmannin can block the PI3 K signal transduction pathway, and inhibit the release of infl ammatory factor TNF-α.
基金supported by grants from Guangdong Medical Research Fund(2010501)Guangzhou Pharmaceutical Health Science Fund(2009-YB-111)
文摘BACKGROUND:Platelet endothelial cell adhesion molecule-1(PECAM-1),also known as CD31,is mainly distributed in vascular endothelial cells.Studies have shown that PECAM-1 is a very significant indicator of angiogenesis,and has been used as an indicator for vascular endothelial cells.The present study aimed to explore the relationship between the expression of PECAM-1 and the degree of acute lung injury(ALI) and fibrosis in paraquat(PQ) induced lung injury in rabbits.METHODS:Thirty-six adult New Zealand rabbits were randomly divided into three groups(12rabbits in each group) according to PQ dosage:8 mg/kg(group A),16 mg/kg(group B),and 32 mg/kg(group C).After PQ infusion,the rabbits were monitored for 7 days and then euthanized.The lungs were removed for histological evaluation.Masson staining was used to determine the degree of lung fibrosis(LF),and semi-quantitative immune-histochemistry analysis to determine the expression of PECAM-1.Pearson's product-moment correlation analysis was performed to evaluate the relationship between the expression of PECAM-1 and the extent of lung injuries expressed by ALI score and degree of LF.RESULTS:Rabbits in the three groups showed apparent poisoning.The rabbits survived longer in group A than in groups B and C(6.47±0.99 days vs.6.09±1.04 days vs.4.77±2.04 days)(P<0.05).ALI score was lower in group A than in groups B and C(8.33±1.03 vs.9.83±1.17 vs.11.50±1.38)(P<0.05),and there was statistically significant difference between group B and group C(P=0.03).LF was slighter in group A than in groups B and C(31.09%±2.05%vs.34.37%±1.62%vs.36.54%±0.44%)(P<0.05),and there was statistically significant difference between group B and group C(P=0.026).The PEACAM-1 expression was higher in group A than in groups B and C(20.31%±0.70%vs.19.34%±0.68%vs.18.37%±0.46%)(P<0.05),and there was statistically significant difference between group B and group C(P=0.017).Pearson's correlation analysis showed that the expression of PECAM-1 was negatively correlated to both ALI score(Coe=-0.732,P=0.001)and degree of LF(Coe=-0.779,P<0.001).CONCLUSIONS:The PECAM-1 expression significantly decreases in New Zealand rabbits after PQ poisoning,and the decrease is dose-dependent.The PECAM-1 expression is negatively correlated with ALI score and LF,showing a significant role in the development of lung injuries induced by PQ.
文摘Acute lung injury （ALl） or acute respiratory distress syndrome （ARDS） can be associated with various disorders. Recent investigation has involved clinical studies in collaboration with clinical investigators and pathologists on the pathogenetic mechanisms of ALl or ARDS caused by various disorders. This literature review includes a brief historical retrospective of ALI/ARDS, the neurogenic pulmonary edema due to head injury, the long-term experimental studies and clinical investigations from our laboratory, the detrimental role of NO, the risk factors, and the possible pathogenetic mechanisms as well as therapeutic regimen for ALI/ARDS.
基金supported by grants from the Shanghai Health Bureau issues(2007102)
文摘BACKGROUND： Mechanical ventilation is a double-edged sword to acute respiratory distress syndrome （ARDS） including lung injury, and systemic inflammatory response high tidal volumes are thought to increase mortality. The objective of this study is to evaluate the effects of dynamic ventilatory factors on ventilator induced lung injury in a dog model of ARDS induced by hydrochloric acid instillation under volume controlled ventilation and to investigate the relationship between the dynamic factors and ventilator-induced lung injuries （VILI） and to explore its potential mechanisms.METHODS： Thirty-six healthy dogs were randomly divided into a control group and an experimental group. Subjects in the experimental group were then further divided into four groups by different inspiratory stages of flow. Two mL of alveolar fluid was aspirated for detection of IL-8 and TNF-α. Lung tissue specimens were also extracted for total RNA, IL-8 by western blot and observed under an electronic microscope.RESULTS： IL-8 protein expression was significantly higher in group B than in groups A and D. Although the IL-8 protein expression was decreased in group C compared with group B, the difference was not statistically significant. The TNF-a ray degree of group B was significantly higher than that in the other groups （P〈0.01）, especially in group C （P〉0.05）. The alveolar volume of subjects in group B was significantly smaller, and cavity infiltration and cell autolysis were marked with a significant thicker alveolar septa, disorder of interval structures, and blurring of collagenous and elastic fiber structures. A large number of necrotic debris tissue was observed in group B.CONCLUSION： Mechanical ventilation with a large tidal volume, a high inspiratory flow and a high ventilation frequency can cause significant damage to lung tissue structure. It can significantly increase the expression of TNF-α and IL-8 as well as their mRNA expression. Furthermore, the results of our study showed that small tidal ventilation significantly reduces the release of proinflammatory media. This finding suggests that greater deterioration in lung injury during ARDS is associated with high inspiratory flow and high ventilation rate.
文摘Objective. To approach the relation and the possible mechanism between the expression of intercellular adhesion molecule (ICAM1) mRNA and acute lung injury (ALI) and the mechanisms of rhubarb in the prevention and treatment of the lung injury. Methods. Lipopolysaccharide (LPS) was injected into the sublingual vein of male Wistar rats to perform ALI animal model. The rats were divided into 4 groups: LPS group, control group, rhubarb group and dexamethasone group. Macroscopic and histopathological examinations were performed and biological markers were measured for the lung specimens. The markers included lung wet/dry weight, the rate of neutrophils and protein content in the pulmonary alveolar lavage fluid, pulmonary vascular permeability and pulmonary alveolar permeability index. Molecular hybridization method was used to determine the expression of ICAM1 mRNA. Results. In the lung tissues, the ICAM1 mRNA expression was increased in the endothelial cells of pulmonary veins and capillaries, rhubarb and dexamethasone had the action of decreasing the expression. The light reflex value in the gray scale scanning showed that in the comparison between the LPS and the control group, the gray scale value of the lung tissues in ALI was significantly increased, thus the light reflex value was markedly decreased (P<001), demonstrating the expression of ICAM1 mRNA was increased. In comparison with the LPS group, dexamethasone and rhubarb could decrease the gray scale value of the lung tissue significantly, thus the light reflex value was elevated (P<001, P<005); the corresponding pathologic changes of lung tissues and the biological markers of the lung injury were significantly decreased or ameliorated. Conclusions. The increase of the expression of ICAM1 mRNA in the lung tissues of ALI plays the roles in ALI. The application of rhubarb and dexamethasone can decrease the expression and ameliorate the lung damage; its mechanism is possibly via the inhibition of ICAM1 mRNA expression.
文摘BACKGROUND: The present study was undertaken to examine the regulatory effect of hydrogen sulfide(H2S) on endoplasmic reticulum stress in alveolar epithelial cells of rats with acute lung injury(ALI) induced by oleic acid(OA).METHODS: Seventy-two male Sprague Dawley(SD) rats were divided into control group, oleic acid-induced ALI group(OA group), oleic acid-induced ALI with sodium hydrosulfide(Na HS) pretreatment group(OA+Na HS group), and sodium hydrosulfide treatment group(Na HS group). Rats of each group were further subdivided into 3 subgroups. Index of quantitative assessment of histological lung injury(IQA), wet/dry weight ratio(W/D) and H2 S level of lung tissues were measured. The expressions of endoplasmic reticulum stress markers including glucose-regulated protein 78(GRP78) and α-subunit of eukaryotic translation initiation factor-2(el F2α) in lung tissues were measured by immunohistochemical staining and Western blotting.RESULTS: The IQA score and W/D ratio of lung tissues at the three time points significantly increased in rats injected with OA, but significantly decreased in other rats injected with OA and Na HS. The level of H2 S in lung tissue at the three time points significantly decreased in rats injected with OA, but significantly increased in other rats injected with both OA and Na HS. GRP78 and el F2α decreased in rats injected with OA, but increased in other rats injected with both OA and Na HS, especially at 4-hour and 6-hour time points.CONCLUSION: The results suggested that H2 S could promote alveolar epithelial cell endoplasmic reticulum stress in rats with ALI.
基金Supported in part by Jie-shou Li Academician Gut Barrier Research Fund(2012001)
文摘Objective To explore whether the amount of lipocalin-2 in the biofluid could reflect the onset of sepsis-induced acute lung injury(ALI) in mice. Methods Lipopolysaccharide(LPS, 10 mg/kg) injection or cecal ligation and puncture(CLP) was performed to induce severe sepsis and ALI in C57 BL/6 male mice randomly divided into 5 groups(n=10 in each group): group A(intraperitoneal LPS injection), group B(intravenous LPS injection via tail vein), group C(CLP with 25% of the cecum ligated), group D(CLP with 75% of the cecum ligated), and the control group(6 sham-operation controls plus 4 saline controls). All the mice received volume resuscitation. Measurements of pulmonary morphological and functional alterations were used to identify the presence of experimental ALI. The expressions of lipocalin-2 and interleukin(IL)-6 in serum, bronchoalveolar lavage fluid(BALF), and lung tissue were quantified at both protein and mRNA levels. The overall abilities of lipocalin-2 and IL-6 tests to diagnose sepsis-induced ALI were evaluated by generating receiver operator characteristic curves(ROC) and computing area under curve(AUC). Results In both group B and group D, most of the "main features" of experimental ALI were reproduced in mice, while group A and group C showed septic syndrome without definite evidence for the presence of ALI. Compared with septic mice without ALI(group A+group C), lipocalin-2 protein expression in septic mice with ALI(group B+group D) was significantly up-regulated in BALF(P<0.01) and in serum(P<0.01), and mRNA expression boosted in lung tissues(all P<0.05). Lipocalin-2 tests performed better than IL-6 tests in recognizing sepsis-induced ALI cases, evidenced by the larger AUC of the former(BALF tests, 0.8800 versus 0.6625; serum tests, 0.8500 versus 0.7000). Using a dual cutoff system to diagnose sepsis-induced ALI, BALF lipocalin-2 test exhibited the highest positive likelihood ratio(13.000) and the lowest negative likelihood ratio(0.077) among the tests of lipocalin-2 and IL-6 in blood and BALF. A statistically significant correlation was found between lipocalin-2 concentration in BALF and that in serum(Spearman r=0.8803,P<0.0001). Conclusions Lipocalin-2 expression is significantly up-regulated in septic ALI mice compared with those without ALI. Lipocalin-2 tests with a dual cutoff system could be an effective tool in distinguishing experimental ALI cases.
文摘BACKGROUND： This study was undertaken to determine the effect of mesenchymal stem cells （MSCs） engraftment on vascular endothelial cell growth factor （VEGF） in lung tissue, plasma and extravascular lung water at early stage of smoke inhalation injury.METHODS： A rabbit smoke inhalation injury model was established using a home-made smoke inhalation injury generator, and rabbits were divided into two groups randomly： a control group （S group, n=32） and a MSCs treatment group （M group, n=32）. 10 ml PBS was injected via the ear marginal vein immediately at injury into the S group. Third generation MSCs with a concentration of 1×107/10 ml PBS were injected via the ear marginal vein immediately at injury into the M group. VEGF in peripheral blood and lung tissue were measured at 0 （baseline）, 2, 4 and 6 hours after injection respectively and analyzed. The right lungs of rabbits were taken to measure lung water mass fraction.RESULTS： In the lung tissue, VEGF decreased gradually in the S group （P〈0.05） and signi？ cantly decreased in the M group （P〈0.05）, but it increased more signi？ cantly than the values at the corresponding time points （P〈0.05）. In peripheral blood, VEGF increased gradually in the S group （P〈0.05） and markedly increased in the M group （P〈0.05）, but it decreased more signi？ cantly than the values at corresponding time points （P〈0.05）.CONCLUSION： MSCs engraftment to smoke inhalation injury could increase VEGF in lung tissue, decrease VEGF in plasma and reduce extravascular lung water, indicating its protective effect on smoke inhalation injury.
文摘Objective: To explore the effects of altitude hypoxia on septic pulmonary injury (3080 m above sea level). Methods : A model of pyosepticemia was established by cecal ligation and puncture. Thromboxane A2 (TXA2),prostacyclin (PGI2) of the venous plasma and leucine-enkephalins (L-ENK) in the arterial walls were measured using radioiizimunoassay in 31 rabbits. Mouse morrality was observed. Results: 24 h mouse accumulative mortality (97. 1% )was greater than that of control (35%). TXB2 content was 4 times as much as in control group and 6-keto-PGF1α level was elevated too. These changes of arachidonic metabolism could be blorked by indomethacin. The contents of LENK in arterial walls of puhiionary, mesenteric and renal arteries dropped significantly in comparison with control group (P<0. 01 ). The albumin content in the bronchoalveolar lavage fluid rase significantly in comparison with control group (P<0. 01 ). Conclusion : The results demonstrate that the metabolites of cyclcoxygenase are not the major mediator of puhiionary permeability in the experiment. The alteration of TXA2 and L-ENK contents may be one of the mechanisms, by which the puhiionary artery pressure and pulmonary vascular resistance are increased during sepsis.
基金supported by the Youth Incubation Project from the Sanitary Bureau of Logistics Security Ministry of the Central Military Commission(19QNP025)Major Applied Basic Research Project from the Logistics Security Ministry of the Central Military Commission(AKJ15J001)。
文摘Background:Aeromedical evacuation of patients with burn trauma is an important transport method in times of peace and war,during which patients are exposed to prolonged periods of hypobaric hypoxia;however,the effects of such exposure on burn injuries,particularly on burn-induced lung injuries,are largely unexplored.This study aimed to determine the effects of hypobaric hypoxia on burn-induced lung injuries and to investigate the underlying mechanism using a rat burn model.Methods:A total of 40 male Wistar rats were randomly divided into four groups(10 in each group):sham burn(SB)group,burn in normoxia condition(BN)group,burn in hypoxia condition(BH)group,and burn in hypoxia condition with treatment intervention(BHD)group.Rats with 30%total body surface area burns were exposed to hypobaric hypoxia(2000 m altitude simulation)or normoxia conditions for 4 h.Deoxyribonuclease I(DNase I)was administered systemically as a treatment intervention.Systemic inflammatory mediator and mitochondrial deoxyribonucleic acid(mtDNA)levels were determined.A histopathological evaluation was performed and the acute lung injury(ALI)score was determined.Malonaldehyde(MDA)content,myeloperoxidase(MPO)activity,and the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3(NLRP3)inflammasome level were determined in lung tissues.Data among groups were compared using analysis of variance followed by Tukey’s test post hoc analysis.Results:Burns resulted in a remarkably higher level of systemic inflammatory cytokines and mtDNA release,which was further heightened by hypobaric hypoxia exposure(P<0.01).Moreover,hypobaric hypoxia exposure gave rise to increased NLRP3 inflammasome expression,MDA content,and MPO activity in the lung(P<0.05 or P<0.01).Burn-induced lung injuries were exacerbated,as shown by the histopathological evaluation and ALI score(P<0.01).Administration of DNase I markedly reduced mtDNA release and systemic inflammatory cytokine production.Furthermore,the NLRP3 inflammasome level in lung tissues was decreased and burn-induced lung injury was ameliorated(P<0.01).Conclusions:Our results suggested that simulated aeromedical evacuation further increased burn-induced mtDNA release and exacerbated burn-induced inflammation and lung injury.DNase I reduced the release of mtDNA,limited mtDNA-induced systemic inflammation,and ameliorated burn-induced ALI.The intervening mtDNA level is thus a potential target to protect from burn-induced lung injury during aeromedical conditions and provides safer air evacuations for severely burned patients.
文摘Low tidal volume mechanical ventilation is difficult to correct hypoxemia, and prolonged inhalation of pure oxygen can lead to oxygen poisoning. We suggest that continuous tracheal gas insufflation （TGI） during protective mechanical ventilation could improve cardiopulmonary function in acute lung injury. Totally 12 healthy juvenile piglets were anesthetized and mechanically ventilated at PEEP of 2 cmH2O with a peak inspiratory pressure of 10 cmH2O. The piglets were challenged with lipopolysaccharide and randomly assigned into two groups （n=6 each group）： mechanical ventilation （MV） alone and TGI with continuous airway flow 2 I/min. FIO2 was set at 0.4 to avoid oxygen toxicity and continuously monitored with an oxygen analyzer. Tidal volume, ventilation efficacy index and mean airway resistant pressure were significantly improved in the TGI group （P〈0.01 or P〈0.05）. At 4 hours post ALl, pH decreased to below 7.20 in the MV group, and improved in the TGI group （P〈0.01）. Similarly, PaCO2 was stable and was significantly lower in the TGI group than in the MV group （P〈0.01）. PaO2 and PaO2/FIO2 increased also in the TGI group （P〈0.05）. There was no significant difference in heart rate, respiratory rate, mean artery pressure, central venous pressure, dynamic lung compliance and mean resistance of airway between the two groups. Lung histological examination showed reduced inflammation, reduced intra- alveolar and interstitial patchy hemorrhage, and homogenously expanded lungs in the TGI group. Continuous TGI during MV can significantly improve gas exchange and ventilation efficacy and may provide a better treatment for acute lung injury.
基金Partly supported by a grant from Jie-shou Li Academician Gut Barrier Research Fund
文摘Objective To determine whether the onset of acute lung injury （ALl） induces the up-regulation of pentraxin 3 （PTX3） expression in mice and whether PTX3 concentration in the biofluid can help recognizing sepsis-induced ALI. Methods Wild-type C57BL/6 mice （12-14 weeks old） were randomly divided into 3 groups. Mice in the group 1 （n=12） and group 2 （n=12） were instilled with lipopolysaccharide via intratracheal or intraperitoneal routes, respectively. Mice in the group 3 （n=8） were taken as blank controls. Pulmonary morphological and functional alterations were measured to determine the presence of experimental ALl. PTX3 expression in the lung was quantified at both protein and mRNA levels. PTX3 protein concentration in blood and bronchoalveolar lavage fluid was measured to evaluate its ability to diagnose sepsis-induced ALI by computing area under receiver operator characteristic curve （AUROCC）. Results ALl was commonly confirmed in the group 1 but never in the other groups. PTX3 expression was up-regulated indiscriminately among lipopolysaccharide-challenged mice. PTX3 protein concentration in the biofluid was unable to diagnose sepsis-induced ALl evidenced by its small AUROCC. PTX3 concentration in bronchoalveolar lavage fluid did not correlate with that in serum. Conclusions Lipopolysaccharide challenges induced PTX3 expression in mice regardless of the presence ofALI. PTX3 may act as an indicator of inflammatory response instead of organ injury per se.
文摘In cases of severe sepsis and septic shock, a series of pathophysiological changes lead to multiple organ dysfunction syndrome.This study aimed to investigate the expression of glucocorticoid receptor mRNA in the rat lung following endotoxin （LPS） induced shock. Totally 56 SD rats were randomly divided into 4 groups： LPS shock group （n=16）, LPS＋vasoactive intestinal peptide group（VIP） group, （n=16）, LPS＋VIP＋ glucocorticoid （GC） group, （n=16）,and control group （n=8）. LPS shock was induced by intravenous injection of LPS （10 mg/kg） in rats. Within 15 minutes after LPS injection, rats in the treatment groups received VIP （5 nmol/kg） or VIP and methylprednisolone （3 mg/kg）. The control group was given normal saline instead of LPS. The rats of the four groups were sacrificed at 6 hours,24 hours after injection respectively, and the lung tissues were collected. Pathological changes of the lungs were examined by light microscopy and electron microscopy. GRmRNA expression in the lung tissues was evaluated by RT-PCR. In the LPS shock group, lung histopathology demonstrated destruction of the alveolar space,widening of the inter-alveolar space, inflammatory cell infiltration and interstitial edema. However,pathological changes in the LPS＋ VIP group and LPS＋ VIP＋GC group were milder than those in the LPS shock group. Six hours after LPS injection, GR mRNA expression was down-regulated in the LPS group （0.72± 0.24） and LPS＋ VIP group （0.88±0.27） （P〈0.05） as compared with the control group （1.17±0.22）. The LPS shock group showed a more significant down-regualtion than the LPS＋VIP group, but the difference was not statistically significant （P〉0.05）. In contrast, GRmRNA expression in the LPS＋ VIP＋GC group was significantly up-regulated at 6 hours and further at 24 hours （1.45±0.32 and 1.91±0.46 respectively） （P〈0.05）. GrmRNA expression decreased in LPS induced lung injury in rats. Combined treatment with VIP and GC mitigated lung injury ang inflammation. The mechanism may be related to up-regulation of GR mRNA expression.
文摘BACKGROUND： This study aimed to observe the effect of recruitment maneuver （RM） and post-RM ventilation at different tidal volume on lung vascular diastole endothelial function in rats with acute lung injury （ALI）.METHODS： A ALl rat model was produced by intravenous infusion of lipopolysaccharide （6 mg/ kg）. Twenty-five rats were randomly divided into five groups： control group （n=5）, ALl group （n=5）, low tidal volume group （LV group, VT 6 mL/kg, n=5）, sustained inflation （SI） with low tidal volume group （SI＋LV group, VT 6 mL/kg, n=5）, and SI with moderate tidal volume group （SI＋MV group, VT 12 mL/ kg, n=5）. RM was performed with SI, airway pressure 30 cmH2O for 30 seconds, and positive end- expiratory pressure （PEEP） was set to 5 cmH2O. Lung tissue was taken after 5 hours of mechanical ventilation. Mean arterial blood pressure （MAP） was monitored during the experiment. Endothelin-1 （ET-1）, endothelial nitricoxide synthase （eNOS）, Ach-induced endothelium-dependent relaxation response of isolated pulmonary artery rings were determined at 5 hours. RESULTS：LPS increased ET-1 level, decreased the expression of eNOS in lung tissue, impaired the Ach-induced endothelium-dependent relaxation response in the pulmonary artery, without obvious effect on systemic hemodynamics. SI＋LV significantly reduced LPS-induced elevation of ET-1 level, increased the expression of eNOS, significantly improved endothelial dysfunction, and improved the dysfunction of endothelium-dependent relaxation in the pulmonary artery. CONCLUSIONS：RM with a high or low tidal volume ventilation could improve the lung vascular endothelial function of rats with acute lung injury, and RM with low tidal volume ventilation could lower significantly the injury of lung vascular endothelial diastole function in rats with acute lung injury.
文摘BACKGROUND： Myeloid cell （TREM-1） is an important mediator of the signal transduction pathway in inflammatory response. In this study, a mouse model of acute lung injury （ALl） by intraperitoneal injection of lipopolysaccharide （LPS） was established to observe the expression pattern of TREM-1 in lung tissue and the role of TREM-1 in pulmonary inflammatory response to ALl.METHODS： Thirty BALB/C mice were randomly divided into a normal control group （n=6） and an ALl group （n=24）. The model of ALl was made by intraperitonal injection of LPS in dose of 10 mg/ kg. Specimens from peripheral blood and lung tissue were collected 6, 12, 24 and 48 hours after LPS injection. RT-PCR was used to detect TREM-1 mRNA, and ELISA was employed for detection of TREM-1 protein and TNF-a protein, and HE staining was performed for the pathological Smith lung scoring under a light microscope.RESULTS： The expressions of TREM-1 mRNAin lung tissue and blood of the ALl group 6, 12, 24, and 48 hours after injection of LPS were higher than those in the control group. The levels of TREM- 1 protein and the levels of TNF-a protein in lung tissue of the ALl group 6, 12, 24, and 48 hours after LPS injection were higher than those of the control group; the level of TREM-1 protein peaked 12 hours after LPS injection, but it was not significantly correlated with the expression of TREM-1 mRNA （P=0.14）; the TNF-a concentration was positively correlated with TREM-1 levels in lung tissue and with Smith pathological score （r=0.795, P=0.001 ：r=0.499, P=0.034）, but not with the expression of TREM-1 mRNA （P=0.176）.CONCLUSION： The expression of TREM-1 mRNA in lung tissue of mice with ALl is elevated, and the expression of TREM-1 mRNA is related to the level of TNF-a and the severity of inflammatory response to ALl. The expressions of the TREM-1 gene are not consistent with the levels of TREM-1 protein, suggesting a new functional protein involved in immune regulation.
文摘We studied the functional changes of pulmonary surfactant （PS） in acutelung injury models produced by endotoxin injection (E.coli O<sub>55</sub>B<sub>5</sub>) in rats.The sur-face properties of the lung lavage liquid and the total phospholipids （TPL） ex-tracted from it were assessed on a modified Wilhelmy film balance.γ-A isothermof the lavage liquid revealed an increase in minimum surface tension and a de-crease in hysteresis area,recruitment index and stability index,whereas that ofTPL extracted from it did not show any change except for hysteresis area.Thesurface activity correlates positively with the TPL content but negatively with thetotal protein content in the lavage liquid.The findings indicated that there was adysfunction of PS in rats with the lung injury induced by endotoxin,suggestingthat the function deficiency of PS might be caused by decreased phospholipidsand increased proteins in the alveoli.
文摘We tried to clarify the role of oxygen radicals released from granulocytes stimulated byphorbol myristate acetate(PMA) in rat acute lung injury. It was found that DNA strand-breakdamage(DSBD) in peripheral white blood cells (WBC) was significantly increased 40 min after injec-tion of PMA. DSBD in lung tissue of rats treated with PMA was also markedly increased comparedwith the controls. The PMA-treated rats showed significantly higher lipid-peroxide (LPO) level inplasma and lung tissue hemogenate than the controls did. These results suggest that determination ofDSBD, a simple and sensitive indicator for oxygen radical damaging, might be useful in thediagnosis of adult respiratory distress syndrome (ARDS), when it is used together with themeasurement of plasma LPO.
文摘Changes of pulmonary α1-and βadrenergic receptors (α1- ARs and β-ARs) after endotoxin-induced lung injury were dynamically observed with radioligand binding assay and the pulmonary rnicrovascular permeability and histopathology were also studied in rats to investigate the relationship between changes of pu1monary ARs and acute lung injury. It was found that the contents of both α1-ARs and β-ARs were significantly decreased after endotoxin-induced acute lung injury. On the basis of these findings, the authors inferred that the down regulation of β-ARs might be one of the factors to increase pulmonary microvascular permeability and that of α1-ARs seems to be a protective reaction. This inference might serve as the theoretical basis to treat pulmonary edema with α1-antagonists and β-agonists clinically.
