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
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: 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
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
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
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
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
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
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
Acute lung injury(ALI)and acute respiratory distress syndrome(ARDS)are common life-threatening lung diseases associated with acute and severe inflammation.Both have high mortality rates,and despite decades of research...Acute lung injury(ALI)and acute respiratory distress syndrome(ARDS)are common life-threatening lung diseases associated with acute and severe inflammation.Both have high mortality rates,and despite decades of research on clinical ALI/ARDS,there are no effective therapeutic strategies.Disruption of alveolar-capillary barrier integrity or activation of inflammatory responses leads to lung inflammation and injury.Recently,studies on the role of extracellular vesicles(EVs)in regulating normal and pathophysiologic cell activities,including inflammation and injury responses,have attracted attention.Injured and dysfunctional cells often secrete EVs into serum or bronchoalveolar lavage fluid with altered cargoes,which can be used to diagnose and predict the development of ALI/ARDS.EVs secreted by mesenchymal stem cells can also attenuate inflammatory reactions associated with cell dysfunction and injury to preserve or restore cell function,and thereby promote cell proliferation and tissue regeneration.This review focuses on the roles of EVs in the pathogenesis of pulmonary inflammation,particularly ALI/ARDS.展开更多
Objective:To study the pathogenesis of acute lung injury in severe acute pancreatitis (SAP). Methods:Rats were sacrificed at 1, 3, 5, 6, 9 and 12 h after establishment of inducing model. Pancreas and lung tissues were...Objective:To study the pathogenesis of acute lung injury in severe acute pancreatitis (SAP). Methods:Rats were sacrificed at 1, 3, 5, 6, 9 and 12 h after establishment of inducing model. Pancreas and lung tissues were obtained for pathological study, microvascular permeability and MPO examination. Gene expressions of TNF-α and ICAM-1 in pancreas and lung tissues were detected by RT-PCR. Results:After inducing SAP model, the injury degree of the pancreas and the lung increased gradually, accompanied with gradually increased MPO activity and microvascular permeability. Gene expressions of TNF-α and ICAM-1 in pancreas rose at 1 h and reached peak at 7 h. Relatively, their gene expressions in the lungs only rose slightly at 1 h and reached peak at 9-12 h gradually. Conclusion:There is an obvious time window between SAP and lung injury, when earlier protection is beneficial to prevent development of acute lung injury.展开更多
BACKGROUND： Paraquat （PQ） is an effective herbicide and is widely used in agricultural production, but PQ poisoning is frequently seen in humans with the lung as the target organ. Clinically pulmonary pathological ...BACKGROUND： Paraquat （PQ） is an effective herbicide and is widely used in agricultural production, but PQ poisoning is frequently seen in humans with the lung as the target organ. Clinically pulmonary pathological changes are often used to predict the severity and prognosis of the patients. In this study, we observed the expression of heat shock protein 70 （HSP70） in rat lung after PQ poisoning and to investigate the therapeutic effects of ulinastatin.METHODS： Seventy-two adult healthy SD rats were randomly divided into a control group （group A, n=24）, a poisoning group （group B, n=24）, and an ulinastatin group （group C, n=24）. The rat models of acute PQ poisoning were established by intra-gastric administration of 80 mg/kg PQ to rats of groups B and C, and the rats of group C were intra-peritoneally injected with 100 000 IU/kg ulinastatin 30 minutes after poisoning. The expression of HSP70 in lung tissue was observed, and W/D and histopathological changes in the lung tissue were compared 12, 24, 48 and 72 hours after poisoning. The expression of HSP70 in the lung tissue was assayed by using RT-PCR. All quantitative data were processed with one-way analysis of variance to compare multiple sample means.RESULTS： Compared to group A, the expression of HSP70 in the lung of rats in groups B and C increased signi？ cantly at all intervals （P〈0.05）. The pathological changes in lung tissue of rats with PQ poisoning included congestion, leukocytes in？ ltration and local hemorrhage, whereas those of group C were signi？ cantly lessened.CONCLUSION： Ulinastatin may ameliorate acute lung injury to some extent after PQ poisoning in rats by enhancing the expression of HSP70.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
BACKGROUND: This study was undertaken to observe the concentration of SP-A/B and the pulmonary surfactant in the lung tissue of rats with acute lung injury/acute respiratory distress syndrome caused by paraquat poison...BACKGROUND: This study was undertaken to observe the concentration of SP-A/B and the pulmonary surfactant in the lung tissue of rats with acute lung injury/acute respiratory distress syndrome caused by paraquat poisoning after the treatment of metabolic antioxidant-lipoic acid and whether its influence was related to TNF-α.METHODS: Sixty-six male Sprage-Dawley rats were randomly divided into three groups: normal control group(NS group), 6 rats; paraquat poisoning group(PQ group), 30 rats; and paraquat+lipoic acid treatment group(LA group), 30 rats. The rats in the PQ and LA groups were subdivided into 3-, 6-, 12-, 24-, 48-hour subgroups, with 6 rats in each group. After the rats were sacrificed, lung tissue from the same part was taken from the rats. After HE staining, histological changes were observed in the tissue under a light microscope. Lung tissue was also taken to test the levels of superoxide dismutase(SOD) and malondialdehyde(MDA). Whole blood(0.8 mL) without anticoagulant was drawn from the tail vein of rats for the determination of the TNF-α level. The total RNA of the lung tissue was collected, and the Rt-PCR method was used to measure the levels of SP-A and SP-B mRNA.RESULTS: HE staining showed that histopathological changes were milder in the LA group than in the PQ group. There were significant differences in MDA and SOD levels between different intervals both in intergroups and intragroups except the 3-hour subgroup(P<0.01). Likewise, the significant differences in the levels of TNF-α were also present between the three groups and between different intervals(P<0.01). The significant differences in SP-A mRNA and SP-B mRNA amplification ratio were seen between the three groups at the same intervals(P<0.01), but the differences between different intervals in the PQ group were statistically significant(P<0.05). The differences between different intervals in the LA group were statistically significant(P<0.01).CONCLUSION: Lipoic acid in acute paraquat poisoning could diminish lung tissue damage by regulating directly tumor necrosis factor and indirectly the content of pulmonary surfactant so as to reduce pulmonary edema, improve lung compliance, and finally protect lung tissues.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.
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.
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 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.
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.
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.
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.
基金This work was supported by the Weatherhead Endowment Fund
文摘Acute lung injury(ALI)and acute respiratory distress syndrome(ARDS)are common life-threatening lung diseases associated with acute and severe inflammation.Both have high mortality rates,and despite decades of research on clinical ALI/ARDS,there are no effective therapeutic strategies.Disruption of alveolar-capillary barrier integrity or activation of inflammatory responses leads to lung inflammation and injury.Recently,studies on the role of extracellular vesicles(EVs)in regulating normal and pathophysiologic cell activities,including inflammation and injury responses,have attracted attention.Injured and dysfunctional cells often secrete EVs into serum or bronchoalveolar lavage fluid with altered cargoes,which can be used to diagnose and predict the development of ALI/ARDS.EVs secreted by mesenchymal stem cells can also attenuate inflammatory reactions associated with cell dysfunction and injury to preserve or restore cell function,and thereby promote cell proliferation and tissue regeneration.This review focuses on the roles of EVs in the pathogenesis of pulmonary inflammation,particularly ALI/ARDS.
文摘Objective:To study the pathogenesis of acute lung injury in severe acute pancreatitis (SAP). Methods:Rats were sacrificed at 1, 3, 5, 6, 9 and 12 h after establishment of inducing model. Pancreas and lung tissues were obtained for pathological study, microvascular permeability and MPO examination. Gene expressions of TNF-α and ICAM-1 in pancreas and lung tissues were detected by RT-PCR. Results:After inducing SAP model, the injury degree of the pancreas and the lung increased gradually, accompanied with gradually increased MPO activity and microvascular permeability. Gene expressions of TNF-α and ICAM-1 in pancreas rose at 1 h and reached peak at 7 h. Relatively, their gene expressions in the lungs only rose slightly at 1 h and reached peak at 9-12 h gradually. Conclusion:There is an obvious time window between SAP and lung injury, when earlier protection is beneficial to prevent development of acute lung injury.
文摘BACKGROUND： Paraquat （PQ） is an effective herbicide and is widely used in agricultural production, but PQ poisoning is frequently seen in humans with the lung as the target organ. Clinically pulmonary pathological changes are often used to predict the severity and prognosis of the patients. In this study, we observed the expression of heat shock protein 70 （HSP70） in rat lung after PQ poisoning and to investigate the therapeutic effects of ulinastatin.METHODS： Seventy-two adult healthy SD rats were randomly divided into a control group （group A, n=24）, a poisoning group （group B, n=24）, and an ulinastatin group （group C, n=24）. The rat models of acute PQ poisoning were established by intra-gastric administration of 80 mg/kg PQ to rats of groups B and C, and the rats of group C were intra-peritoneally injected with 100 000 IU/kg ulinastatin 30 minutes after poisoning. The expression of HSP70 in lung tissue was observed, and W/D and histopathological changes in the lung tissue were compared 12, 24, 48 and 72 hours after poisoning. The expression of HSP70 in the lung tissue was assayed by using RT-PCR. All quantitative data were processed with one-way analysis of variance to compare multiple sample means.RESULTS： Compared to group A, the expression of HSP70 in the lung of rats in groups B and C increased signi？ cantly at all intervals （P〈0.05）. The pathological changes in lung tissue of rats with PQ poisoning included congestion, leukocytes in？ ltration and local hemorrhage, whereas those of group C were signi？ cantly lessened.CONCLUSION： Ulinastatin may ameliorate acute lung injury to some extent after PQ poisoning in rats by enhancing the expression of HSP70.
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.
基金supported by a grant from the National Natural Science Foundation project of China(30671783)
文摘BACKGROUND: This study was undertaken to observe the concentration of SP-A/B and the pulmonary surfactant in the lung tissue of rats with acute lung injury/acute respiratory distress syndrome caused by paraquat poisoning after the treatment of metabolic antioxidant-lipoic acid and whether its influence was related to TNF-α.METHODS: Sixty-six male Sprage-Dawley rats were randomly divided into three groups: normal control group(NS group), 6 rats; paraquat poisoning group(PQ group), 30 rats; and paraquat+lipoic acid treatment group(LA group), 30 rats. The rats in the PQ and LA groups were subdivided into 3-, 6-, 12-, 24-, 48-hour subgroups, with 6 rats in each group. After the rats were sacrificed, lung tissue from the same part was taken from the rats. After HE staining, histological changes were observed in the tissue under a light microscope. Lung tissue was also taken to test the levels of superoxide dismutase(SOD) and malondialdehyde(MDA). Whole blood(0.8 mL) without anticoagulant was drawn from the tail vein of rats for the determination of the TNF-α level. The total RNA of the lung tissue was collected, and the Rt-PCR method was used to measure the levels of SP-A and SP-B mRNA.RESULTS: HE staining showed that histopathological changes were milder in the LA group than in the PQ group. There were significant differences in MDA and SOD levels between different intervals both in intergroups and intragroups except the 3-hour subgroup(P<0.01). Likewise, the significant differences in the levels of TNF-α were also present between the three groups and between different intervals(P<0.01). The significant differences in SP-A mRNA and SP-B mRNA amplification ratio were seen between the three groups at the same intervals(P<0.01), but the differences between different intervals in the PQ group were statistically significant(P<0.05). The differences between different intervals in the LA group were statistically significant(P<0.01).CONCLUSION: Lipoic acid in acute paraquat poisoning could diminish lung tissue damage by regulating directly tumor necrosis factor and indirectly the content of pulmonary surfactant so as to reduce pulmonary edema, improve lung compliance, and finally protect lung tissues.
