The angiotensin-converting enzyme(ACE)inhibitory peptide NCW derived from Mizuhopecten yessoensis has been demonstrated to have significant in vivo anti-hypertensive effects,however,its anti-hypertensive mechanism is ...The angiotensin-converting enzyme(ACE)inhibitory peptide NCW derived from Mizuhopecten yessoensis has been demonstrated to have significant in vivo anti-hypertensive effects,however,its anti-hypertensive mechanism is still not fully clarified.This study established a UPLC-Q-TRAP-MS/MS-based widely targeted kidney metabolomics approach to explore the changes of kidney metabolic profiles and to clarify the antihypertensive mechanism of peptide NCW in spontaneously hypertensive rats(SHRs).Multivariate statistical analysis indicated that the kidney metabolic profiles were clearly separated between the SHR-NCW and SHRUntreated groups.A total of 85 metabolites were differentially regulated,and 16 metabolites were identified as potential kidney biomarkers,e.g.,3-hydroxybutyrate,malonic acid,deoxycytidine,and L-aspartic acid.The peptide NCW might regulate kidney metabolic disorder of SHRs to alleviate hypertension by suppressing inflammation and improving nitric oxide production under the regulation of linoleic acid metabolism,folate related pathways,synthesis and degradation of ketone bodies,pyrimidine metabolism,β-alanine metabolism,and retinal metabolism.展开更多
BACKGROUND:This study aims to explore whether Xuebijing(XBJ) can improve intestinal microcirculation dysfunction in sepsis and its mechanism.METHODS:A rat model of sepsis was established by cecal ligation and puncture...BACKGROUND:This study aims to explore whether Xuebijing(XBJ) can improve intestinal microcirculation dysfunction in sepsis and its mechanism.METHODS:A rat model of sepsis was established by cecal ligation and puncture(CLP).A total of 30 male SD rats were divided into four groups:sham group,CLP group,XBJ + axitinib group,and XBJ group.XBJ was intraperitoneally injected 2 h before CLP.Hemodynamic data(blood pressure and heart rate) were recorded.The intestinal microcirculation data of the rats were analyzed via microcirculation imaging.Enzyme-linked immunosorbent assay(ELISA) kits were used to detect the serum levels of interleukin-6(IL-6),C-reactive protein(CRP),and tumor necrosis factor-α(TNF-α) in the rats.Histological analysis and transmission electron microscopy were used to analyze the injury of small intestinal microvascular endothelial cells and small intestinal mucosa in rats.The expression of vascular endothelial growth factor A(VEGF-A),phosphoinositide 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),protein kinase B(Akt),and phosphorylated Akt(p-Akt) in the small intestine was analyzed via Western blotting.RESULTS:XBJ improved intestinal microcirculation dysfunction in septic rats,alleviated the injury of small intestinal microvascular endothelial cells and small intestinal mucosa,and reduced the systemic inflammatory response.Moreover,XBJ upregulated the expression of VEGF-A,p-PI3K/total PI3K,and p-Akt/total Akt in the rat small intestine.CONCLUSION:XBJ may improve intestinal microcirculation dysfunction in septic rats possibly through the VEGF-A/PI3K/Akt signaling pathway.展开更多
Ovotransferrin,an iron-binding glycoprotein,accounting for approximately 12%of egg white protein,is a member of transferrin fam ily.Our previous studies showed that ovotransferrin stimulates the proliferation and diff...Ovotransferrin,an iron-binding glycoprotein,accounting for approximately 12%of egg white protein,is a member of transferrin fam ily.Our previous studies showed that ovotransferrin stimulates the proliferation and differentiation of osteoblasts,while inhibits osteoclastogenesis and resorption activity.The work aims to study the efficacy of orally administered ovotransferrin on the prevention of osteoporosis using ovariectomized(OVX)Sprague-Dawley rats.Oral administration of ovotransferrin showed no negative effect on body weight,food intake and organ weight.After 12-week treatment,feeding ovotransferrin at a dose of 1%(1 g ovotransferrin/100 g diet)prevented OVX-induced bone loss and maintained relatively high bone mineral density and integrated bone microarchitecture.The serum concentration of biomarkers indicating bone formation was increased in ovotransferrin administration groups,while the bone resorption biomarkers were decreased.Ovotransferrin feeding also decreased the production of serum cytokine TNF-αand IL-6,which are two stimulators for osteoclast differentiation.In addition to its direct regulatory role on bone turnover,ovotransferrin supplementation might benefit osteoporosis prevention by inhibiting adipogenesis,and regulating immune response.Our results suggested the potential application of ovotransferrin as a functional food ingredient on the prevention of osteoporosis.展开更多
Objective To evaluate the antagonistic effects of N-acetylcysteine(NAC)on mitogen-activated protein kinases(MAPK)pathway activation,oxidative stress and inflammatory responses in rats with lung injury induced by fine ...Objective To evaluate the antagonistic effects of N-acetylcysteine(NAC)on mitogen-activated protein kinases(MAPK)pathway activation,oxidative stress and inflammatory responses in rats with lung injury induced by fine particulate matter(PM2.5).Methods Forty eight male Wistar rats were randomly divided into six groups:blank control group(C1),water drip control group(C2),PM2.5 exposed group(P),low-dose NAC treated and PM2.5 exposed group(L),middle-dose NAC treated and PM2.5 exposed group(M),and high-dose NAC treated and PM2.5 exposed group(H).PM2.5 suspension(7.5 mg/kg)was administered tracheally once a week for four times.NAC of 125 mg/kg,250 mg/kg and 500 mg/kg was delivered intragastrically to L,M and H group respectively by gavage(10 ml/kg)for six days before PM2.5 exposure.The histopathological changes and human mucin 5 subtype AC(MUC5AC)content in lung tissue of rats were evaluated.We investigated IL-6 in serum and bronchoalveolar lavage fluid(BALF)by Enzyme-linked immunosorbent assay(ELISA),MUC5AC in lung tissue homogenate by ELISA,glutathione peroxidase(GSH-PX)in serum and BALF by spectrophotometry,and the expression of p-ERK1/2,p-JNK1/2 and p-p38 proteins by Western blot.All the measurements were analyzed and compared statistically.Results Lung tissue of rats exposed to PM2.5 showed histological destruction and increased mucus secretion of bronchial epithelial cells.Rats receiving NAC treatment showed less histological destruction and mucus secretion.Of P,L,M and H group,MUC5AC in lung tissue,IL-6 in serum and BALF were higher than controls(C1 and C2)(all P<0.05),with the highest levels found in the P group and a decreasing trend with increase of NAC dose.The activity of GSH-PX in serum and BALF of PM2.5 exposed rats(P,L,M and H)was lower than that of controls(all P<0.05),with higher activities found in NAC treated rats(L,M,and H),and an increasing trend with increase of NAC dose.The expressions of p-ERK1/2,p-JNK1/2 and p-p38 proteins in PM2.5 exposed lung tissue(P,L,M and H)was higher than controls(all P<0.05),with decreased levels and dose dependent downregulation found in NAC treated rats.Conclusion NAC can antagonize major MAPK pathway activation,lung oxidative stress and inflammatory injury induced by PM2.5 in rats.展开更多
BACKGROUND： Paraquat （PQ） intoxication causes lung oxidative stress damage. Saturated hydrogen saline, a newly explored antioxidant, has been documented to play a powerful antioxidant role in preventing oxidative s...BACKGROUND： Paraquat （PQ） intoxication causes lung oxidative stress damage. Saturated hydrogen saline, a newly explored antioxidant, has been documented to play a powerful antioxidant role in preventing oxidative stress damage. This study aimed to investigate the protective effects and the possible mechanisms of intoxication on rats with acute lung injury （ALl） caused by paraquat poisoning. METHODS： Thirty PQ poisoned rats were randomly divided into a PQ intoxication group （intoxication group）, a saturated hydrogen saline intervention group （intervention group）, and a control group, with 10 rats in each group. The first two groups accepted an intragastric administration of PQ at a dose of 50 mg/kg for every single rat, and the control group was fed with a same volume of normal saline. Five mL/kg of saturated hydrogen saline was given to the intervention group three times a day by peritoneal injection for three days after intoxication. Arterial blood gas was detected on the third day. The rats were executed and their lungs were taken for measurement of wet dry weight ratio, homogenate malondialdehyde （MDA）, and 8-hydroxy-2＇-deoxyguanosine （8-OhdG）. Histological changes of the lungs were also observed. RESULTS： Compared with the control group, the intoxication group had more serious hypoxemia, greater wet/dry weight ratio, higher MDA level, higher expression of 8-OhdG and more severe lung damage （P〈0.01 or P〈0.05）. However, after intervention with saturated hydrogen saline, poisoned animals turned to have lighter hypoxemia, smaller wet/dry weight ratio, lower MDA level, lower expression of 8-OhdG, and milder lung damage （P〈0.01 or P〈0.05）. CONCLUSIONS： Saturated hydrogen sal by PQ. Possibly, it can neutralize toxic oxygen injury induced by PQ. ne is effective in preventing acute lung injury caused radicals selectively and alleviate the oxidative stress展开更多
Objective To assess the severity and reversibility of the chronic toxicity of a novel recombinant human granulocyte colony-stimulating factor (rhG-CSFa) in rats and the dose-effect relationship.Methods A total of 100 ...Objective To assess the severity and reversibility of the chronic toxicity of a novel recombinant human granulocyte colony-stimulating factor (rhG-CSFa) in rats and the dose-effect relationship.Methods A total of 100 Sprague-Dawley rats (equal numbers of male and female) were randomly divided into five groups (20 rats in each group):four groups were treated with rhG-CSFa at 500,100,10,1 μg/kg,respectively,and one group was treated with vehicle only to serve as the control.The rats were received subcutaneous injections of rhG-CSFa or vehicle daily for 13 weeks.During the course of the chronic toxicity study,the physical status,body weight,and food consumption were monitored.Half of the rats in each group (n=10) were sacrificed after the last rhG-CSFa administration,and the other half were sacrificed at five weeks after the last rhG-CSFa administration.Urinalyses,blood biochemistry,hematological analysis,histopathological examination,and immunological tests were performed for each of the rats.Results The hematological analyses revealed that the mean white blood cells count,neutrophils count,and neutrophils percentage were increased in male rats at the dose of 10 μg/kg or higher,and these were related with the biological activity of rhG-CSFa.Some small abnormalities were observed in the spleen of a few rats when used highest dose (500 μg/kg,a dosage of 200 folds higher than the normal clinical dosage),but these abnormalities were recovered within 5-week recovery period.No other rhG-CSFa-related abnormalities were observed in this chronic toxicity study.Conclusion No significant toxicity and immunogenicity are observed with rhG-CSFa administration to rats in the chronic toxicity studies.展开更多
Objective To investigate the combined effects of chronic obstructive pulmonary disease(COPD)and depression on spatial memory in old rats,aiming to better understand the comorbidity of the two diseases in geriatric pat...Objective To investigate the combined effects of chronic obstructive pulmonary disease(COPD)and depression on spatial memory in old rats,aiming to better understand the comorbidity of the two diseases in geriatric patients.Methods The SD rats were assigned into five groups:adult control group(n=6),elderly control group(n=6),elderly COPD group(n=6),elderly depression group(n=6)and elderly COPD with depression group(n=6).Smoking and chronic unpredictable mild stress(CUMS)with solitary support were used to induce COPD model,depression model,respectively,and the both were applied for the comorbidity model.Learning and memory deficits were assessed by Morris water maze(MWM)test.The activity of superoxide dismutase(SOD)and the content of malondialdehyde(MDA)in serum and hippocampus tissue were determined by Xanthinoxidase method and Thiobarbituric acid reaction(TBAR)method,respectively.Results The results of pulmonary histology,lung function,open-field test and sucrose consumption demonstrated the comorbidity models of COPD and depression in elderly rats were successfully established using smoking and CUMS with solitary support.Compared with the elderly control group,the group of COPD with depression had obviously longer time of latency and longer travel distance to reach the platform in MWM test(LSD-t=-10.116,P=0.000;LSD-t=-6.448,P=0.000).The SOD activity in serum and hippocampus decreased significantly(LSD-t=2.629,P=0.014;LSD-t=2.215,P=0.044)and the MDA content in serum and hippocampus increased significantly(LSD-t=-2.140,P=0.042;LSD-t=-2.070,P=0.049)in elderly COPD with depression group.Conclusions COPD in comorbidity of depression could induce spatial memory deficit in old rats.The mechanisms might be related to the overloaded and free radical metabolic imbalance.These results suggest a potential therapeutic target for comorbidity of COPD and depression in geriatric patients.展开更多
Objective To investigate the antagonistic effects of different doses of Lianhua Qingwen on pulmonary injury induced by fine particulates PM2.5 in rats. Methods Fine particulates suspended in the environment were colle...Objective To investigate the antagonistic effects of different doses of Lianhua Qingwen on pulmonary injury induced by fine particulates PM2.5 in rats. Methods Fine particulates suspended in the environment were collected. Forty-eight healthy adult wistar rats were randomly divided into 6 groups with 8 rats in each group. Four groups of rats were exposed to PM2.5 by intratracheally dripping suspensions of fine particulates PM2.5(7.5 mg/kg) as dust-exposed model rats. Among them 24 rats in three groups received Lianhua Qingwen treatment(crude drug) at a dose of 2 g/kg, 4 g/kg, 8 g/kg per day for 3 days before dust exposure and were defined as low-dose, middle-dose and high-dose Lianhua Qingwen treatment groups respectively. The other dust-exposed model rats without treatment were assigned as PM2.5 control group. The un-exposed rats were set as saline control group(1.5 ml/kg saline) and blank control group. All rats were killed after 24 hours of the exposure. Lung tissue, serum and bronchoalveolar lavage fluid(BALF) were collected. The levels of malonaldehyde(MDA), lactate dehydrogenase(LDH), and glutathione peroxidase(GSH-PX) in blood serum and BALF, and superoxide dismutase(SOD) in blood surum were measured using fluorescent quantitation PCR; Expression of NF-E2-related factor 2(NRF-2), heme oxygenase 1(HO-1) and quinone oxidoreductase 1(NQO1) in lung tissues were measured using Western blot. Pathological changes of lung tissues in each group were also examined. Results Pathology revealed thickened alveolar septum, congestion of capillary, interstitial edema and infiltration of lymphocyte and neutrophil surrounding bronchiole in the PM2.5 control group, which weresignificantly relieved in the Lianhua Qingwen treatment groups. Compared to the blank and saline control groups, the PM2.5 control group had significantly higher levels of LDH and MDA(p<0.01) and lower level of GSH-PS(p<0.01) in BALF, significantly higher levels of LDH and MDA(p<0.05) and lower level of GSH-PS(p<0.05) in rat serum. The levels of MDA in blood serum and BALF were significantly lower in each treatment group than that in PM2.5 control group(all P<0.05). In both middle-dose and high-dose treatment group the measurements of LDH in serum and BALF as well as GSH-PX in serum were significant difference from those of PM2.5 control group(all P<0.05). Expressions of NRF-2, HO-1 and NQO1 in lung tissues were significantly different among middle-dose and high-dose treatment group compared with those in PM2.5 control group(all P<0.05). Conclusion Fine particulates PM2.5 in environment may induce pulmonary oxidative lesions in rats. Middle-dose and high-dose Lianhua Qingwen has antagonist effece on the injuries induced by fine particulates.展开更多
This study was designed to establish an animal model of gastric mucosal precancerous lesions in Wistar rats and on this model, the mechanism to produce the precancerous lesions and their reverse therapy were studied. ...This study was designed to establish an animal model of gastric mucosal precancerous lesions in Wistar rats and on this model, the mechanism to produce the precancerous lesions and their reverse therapy were studied. Ranitidine (R) 0.03% in the diet, N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)50 μg/ml in drinking water, or both of them were administered to Wistar rats for 20 weeks. The iats were maintained without the drugs for additional 23 weeks. A control group of rats without any treatment of drugs were kept for 43 weeks Intestinal metaplasia (IM) was found in 86.5% of the rats in MNNG group, 22.5% in R groupand 100% in MNNG+R while only 7.5% in the control. The incidence of IM was significantly different between MNNG+R group and R group or MNNG group. The number of metaplastic glands was also the highest in the MNNG+R group. The therapeutic effects of retinoic acid (RA) and sodium butyrate (SB) on the iNduced precancerousous lesions of the glandular gastric mucosa were observed. It was found that the incidence of IM, moderate and severe dysplasia, and gastric cancer and the number of metaplastic glands in the pylorus and fundus were significantly lower in RA treated group (72.0%, 24.0%, 0%, 130.2±93.9 and 51.5±39.1) and SB treated gioup (60.0%,20.0%, 0%, 70.3±46.8, and 39.8±29.6) than in the RA untreated group (100%, 52.2%, 16.0%, 442.4±230.0 and 247.4±112.07) and the SB untreated group (88.0%, 48.0%. 16.0%, 241.4±113.9 and 146.4±66.3)(P<0.01 to 0.05). A mucosal flap with vascular pedicle from the gastric wall of the Wistar rats was transplanted to the duodenum, jejunum and colon respectively and the rats were killed in the 3td, 6th, 9th and 12th month after operation. IM was found in all the gastric grafts to the intestines with optical and electron microscopy. It is concluded on the basis of the findings that the concomitant administration of MNNG and R is a reliable method to induce IM of gastric mucosa in rats; RA and SB are efficient agents for the reverse thevapy of the precancerous lesions of gastric glandular mucosa in rats; and the formation of IM of gastric mucosa might be a pH-related process. The possible mechanism of the development of IM was discussed.展开更多
Tumor necrosis factor(TNF) mRNA was determined with dot blotting in various viscera 24 h after severe burn injury in rats. It was found that TNF mRNA was detected in the liver, kidneys, spleen,lungs and small intestin...Tumor necrosis factor(TNF) mRNA was determined with dot blotting in various viscera 24 h after severe burn injury in rats. It was found that TNF mRNA was detected in the liver, kidneys, spleen,lungs and small intestines in normal conditions. After burn in展开更多
The effects of verapamil, a calcium antagonist, on arterial blood pressure and myocardial mitochondrial respiratory function were studied in rats after they were inflicted with 6 Gy irradiation and 30% TBSA full thick...The effects of verapamil, a calcium antagonist, on arterial blood pressure and myocardial mitochondrial respiratory function were studied in rats after they were inflicted with 6 Gy irradiation and 30% TBSA full thickness burns. The preventive or therapeutic administration of verapamil exerted little effects on the arterial blood pressure but could effectively protect the myocardial mitochondrial respiratory function after combined radiation-burn injury in rats.The protective effects of verapamil might exercise through the reduction of calcium content in the mitochondria.展开更多
Objective To investigate the role of Caspase-3 in retinal damage caused by hght exposure in rats. Methods Light injury to retina was induced by persistent exposure to illumination （intensity ： 30 000 ± 50 lux...Objective To investigate the role of Caspase-3 in retinal damage caused by hght exposure in rats. Methods Light injury to retina was induced by persistent exposure to illumination （intensity ： 30 000 ± 50 lux） of operating microscope for 30 minutes in the right eyes of Sprague-Dawley rats. The pathological changes of retina were observed under optical and electron microscopies at different time points, which were 6 hours, 1,3,7, and 15 days after the hght exposure. Apoptosis of retinal cells was analyzed by flow cytometry. The activity of Caspase-3 was evaluated by using the Caspase-3 assay kit. At the same time, the expression of Caspase-3 protease was determined with Western blot analysis. Results The examination results of optical and transmission electron microscopes showed that edema of inner and outer segments of the retina, especially the chondriosome inside the inner segment, became obvious 6 hours after the light exposure. The change was deteriorated along with the increasing time. The structures of the discoidal valve dissociated in the outer segment simultaneously. Disorderly arranged nuclei, karyopycnosis, and thinning in the outer nuclear layer were observed. The retinal pigment epithelium almost disappeared during the later stage. The staining results of Annexin-V combined with PI demonstrated that the proportion of apoptotic cells increased with time. The proportion between 7th day （82.7%） and 15th day （80.4%）, however, showed no significant difference. Caspase-3 became remarkably active with the lapse of time, which increased from 0.02 at 6th hour to the peak of 9. 8 at 7th day before it started to descend. The Western blot detected a expression of the active form of Caspase-3 at 7th day and 15th day. Conclusion Apoptosis of photoreceptor cells is markedly involved in the light damage and Caspase-3 protease may play an important role in the apoptotic process of the retina after light exposure in rats.展开更多
Immunoreactive substance P(Ir-SP)level,and substance P likeimmunoreactivity(SP-Li)in the spinal cord were observed with radioimmunoassay andimmunohistochemistry in rats after they were given an intraperitoneal injecti...Immunoreactive substance P(Ir-SP)level,and substance P likeimmunoreactivity(SP-Li)in the spinal cord were observed with radioimmunoassay andimmunohistochemistry in rats after they were given an intraperitoneal injection of mor-phine(7.5mg/kg)or electroacupunctured(3V and 3Hz)on the “Jiaji point”.It wasfound that the pain threshold(PT),Ir-SP level and SP-Li in the dorsal horn of the spi-nal cord were more significantly increased in the animals after the administration ofmorphine or electroacupuncture than in the control(P【0.05～0.01).The combined effectsof morphine and electropacupuncture were even more powerful than either of the agentswas administered singly.Naloxone could block the analgesic effect and the elevation ofIr-SP due to morphine or electroacupuncture.The findings suggest that there is a synergismbe tween morphine and electroacupuncture and the analgesic effect of the 2 depends uponthe increase of Ir-SP level of the spinal cord mediated through the opiate receptors.展开更多
BACKGROUND:Sepsis-induced myocardial injury is one of the major predictors of morbidity and mortality of sepsis.The cytoprotective function of erythropoietin(EPO) has been discovered and extensively studied.However,th...BACKGROUND:Sepsis-induced myocardial injury is one of the major predictors of morbidity and mortality of sepsis.The cytoprotective function of erythropoietin(EPO) has been discovered and extensively studied.However,the cardioprotective effects of EPO on sepsis-induced myocardial injury in the rat sepsis model has not been reported.METHODS:The rat models of sepsis were produced by cecal ligation and perforation(CLP)surgery.Rats were randomly(random number) assigned to one of three groups(n=8 for each group):sham group,CLP group and EPO group(1000 lU/kg erythropoietin).Arterial blood was withdrawn at3,6,12,and 24 hours after CLP.cTnl,BNP,CK-MB,LDH,AST,TNF-a,IL-6,IL-10,and CRP were tested by the ELISA assay.Changes of hemodynamic parameters were recorded at 3,6,12,24 hours after the surgery.Histological diagnosis was made by hematoxylin and eosin.Flow cytometry was performed to examine cell apoptosis,myocardium mitochondrial inner membrane potential,and NF-κB(p65).Survival rate at 7 days after CLP was recorded.RESULTS:In the CLP group,myocardial enzyme index and inflammatory index increased at3,6,12 and 24 hours after CLP compared with the sham group,and EPO significantly blocked the increase.Compared with the CLP group,EPO significantly improved LVSP,LV +dpldt_(max) LV-dp/dt_(min),and decreased LVEDP at different time.EPO blocked the reduction of mitochondrial transmembrane potential,suppressed the cardiomyocyte apoptosis,inhibited the activation of NF-κB,and reduced the production of proinflmmatory cytokines.No difference in the survival rate at 7 days was observed between the CLP group and the EPO group.CONCLUSION:Exogenous EPO has cardioprotective effects on sepsis-induced myocardial injury.展开更多
The effects of different ambient pressures of 53.99,61.33 and 96.60 kPa on theseverity of blast injury were observed in rats.It was found that when the incident shock wavewas 190.40 kPa in its peak pressure and 10 ms ...The effects of different ambient pressures of 53.99,61.33 and 96.60 kPa on theseverity of blast injury were observed in rats.It was found that when the incident shock wavewas 190.40 kPa in its peak pressure and 10 ms in its duration, both the mortality and the severityof lung injury were progressively increased along with the decrease of the ambient pressure.Themortality rate of the rats in the 6th hour after exposure was 0%,25% and 36.8% and the hem-orrhagic area on the lungs was 63.75+69.01,313.50+357.25 and 653.21+652.25 squaremilimeters when the ambient pressure was 96.60,61.33 and 53.99 kPa respectively.In addi-tion, the lung/body index was 0.93+0.21%,1.31+0.65% and 1.50+0.77% respectively.Itis believed that the decrease of the ambient pressure might decrease the tolerance of the rat to theimpact of blast waves to result in higher mortality and more extensive hemorrhage on the lungs.展开更多
Objective To examine the effects of exogenously administered intermedin （IMD,adrenomedullin-2） on arterial blood pressure,cardiac function and the cardiovascular IMD receptor system in spontaneously hypertensive ra...Objective To examine the effects of exogenously administered intermedin （IMD,adrenomedullin-2） on arterial blood pressure,cardiac function and the cardiovascular IMD receptor system in spontaneously hypertensive rats （SHRs） as well as to investigate the associated mechanisms.Methods Thirteen week-old male rats were divided in Wistar Kyoto （WKY） group （n =12）,SHR group （n =12）,IMD group （SHRs infused with IMD 1-47 500 ng/kg per hour,n =12）,and ADM group （SHRs infused with adrenomedullin 500 ng/kg per hour,n =12）.Results A two-week continuous administration of low dose IMD 1-47 via mini-osmotic pumps markedly reduced blood pressure,the maximal rates of increase and decrease of left-ventricle pressure development （LV ± dp/dtmax）,left ventricular systolic pressure and heart rate in SHRs.Furthermore,IMD also inhibited protein over-expression of cardiovascular IMD receptors,myocardial Receptor Activity-Modifying Proteins （RAMP1 and RAMP2）,aortic RAMP1,RAMP2,RAMP3,and calcitonin receptor-like receptor （CRLR）;suppressed up-regulation of aortic RAMP1,RAMP2,RAMP3 and CRLR gene expression; and markedly elevated the mRNA abundance of myocardial atrial natriuretic peptide （ANP） and myocardial brain natriuretic peptide （BNP）.Additionally,IMD 1-47 administration in SHRs increased aortic cAMP concentration and reduced myocardial cAMP concentration.Conclusion These findings support the speculation that IMD,as a cardiovascular active peptide,is involved in blood pressure reduction and cardiac function amelioration during hypertension.The mechanism underlying this effect may involve IMD binding of a receptor complex formed by RAMPs and CRLR,and consequential regulation of cAMP levels and other cardiovascular active factors,such as ANP and BNP.展开更多
Objective: To establish a stable reduced-size hepatic transplantation model in rats. Methods: Liver transplantation was performed in accordance with Kamada techniques. Many modifications were made including: Surgical ...Objective: To establish a stable reduced-size hepatic transplantation model in rats. Methods: Liver transplantation was performed in accordance with Kamada techniques. Many modifications were made including: Surgical manipulative innovation, adjustment of pre-operative drug administration and removed liver volume. Results: Forty-two rats underwent reduced-size hepatic transplantation; of them 33(84.6%) survived more than 1 week. The causes of postoperative death were peritonitis, inferior vena cava thrombus and unknown complications. Conclusion: Manipulative innovation and proper drug administration can improve the survival rate of rats apparently. Grafts regeneration can be triggered by the removal of left lateral segment and caudate lobe.展开更多
BACKGROUND:This study aims to explore the characteristics of the epithelial-to-mesenchymal transition(EMT)process and its underlying molecular mechanisms in the period of paraquat(PQ)-induced pulmonary fi brosis(PF).M...BACKGROUND:This study aims to explore the characteristics of the epithelial-to-mesenchymal transition(EMT)process and its underlying molecular mechanisms in the period of paraquat(PQ)-induced pulmonary fi brosis(PF).METHODS:Picrosirius red staining and collagen volume fraction were utilized to evaluate the pathological changes of PQ-induced PF in rats.Immunohistochemistry,Western blot,and real-time reverse transcriptase-polymerase chain reaction(RT-PCR)were used to measure the protein and gene expression of EMT markers,EMT-associated transcription factors,and regulators of EMT-related pathways,respectively.RESULTS:The collagen deposition in the alveolar septum and increased PF markers were characteristics of pathological changes in PQ-induced PF,reached a peak on day 14 after PQ poisoning,and then decreased on day 21.The protein and gene expression of the fibrosis marker,EMT markers,transcription factors,and regulators of EMT-related signaling pathways signifi cantly increased at diff erent time points after PQ poisoning compared with corresponding controls(P<0.05),and most of them reached a peak on day 14,followed by a decrease on day 21.The gene expression of EMT markers was significantly correlated with PF markers,transcription factors,and regulators of EMT-related signaling pathways(P<0.05).The mRNA expression of transcription factors was signifi cantly correlated with that of TGF-β1 and Smad2(P<0.05 or P<0.01),instead of Wnt2 andβ-catenin(P>0.05).CONCLUSIONS:EMT process plays a role in the PQ-induced PF,in which most PF and EMT markers have a peak phenomenon,and its underlying molecular mechanisms might be determined by further studies.展开更多
Objective: To establish a model for pregnancy-induced hypertension syndrome in rats. Methods: Adult female Wistar rats were randomized into non-pregnant control (NN), non-pregnant cold-stress control (NC), pregnant co...Objective: To establish a model for pregnancy-induced hypertension syndrome in rats. Methods: Adult female Wistar rats were randomized into non-pregnant control (NN), non-pregnant cold-stress control (NC), pregnant control (PN) and pregnant cold-stress (PC) groups. The rats of NN and PN groups were put under 25 ℃ and those of NC and PC groups under (4±2)℃ for 4 h every morning respectively in the whole experimental period. The blood pressure, urine protein, body weight, haematocrit, weight of the placenta and weight and length of the fetus were recorded and the histological changes of the placenta and the kidneys were also studied. Results: The blood pressure and urine protein of the rats of the NC and PC groups after 2 weeks of cold-stress were more significantly increased than the rats of the NN and PN groups. In addition, the weight of the placenta and the weight and length of the fetus were more significantly lower in the former than the latter. Obvious changes of anoxia and ischemia were observed in the tissues of the kidneys and every layer of the placenta. Conclusion: Our findings of hypertension syndrome induced with repeated cold-stress in pregnant rats can be applied to illustrate the pathogenesis of pregnancy-induced hypertension syndrome in human beings.展开更多
基金supported by the National Natural Science Foundation of China(No.31901635)。
文摘The angiotensin-converting enzyme(ACE)inhibitory peptide NCW derived from Mizuhopecten yessoensis has been demonstrated to have significant in vivo anti-hypertensive effects,however,its anti-hypertensive mechanism is still not fully clarified.This study established a UPLC-Q-TRAP-MS/MS-based widely targeted kidney metabolomics approach to explore the changes of kidney metabolic profiles and to clarify the antihypertensive mechanism of peptide NCW in spontaneously hypertensive rats(SHRs).Multivariate statistical analysis indicated that the kidney metabolic profiles were clearly separated between the SHR-NCW and SHRUntreated groups.A total of 85 metabolites were differentially regulated,and 16 metabolites were identified as potential kidney biomarkers,e.g.,3-hydroxybutyrate,malonic acid,deoxycytidine,and L-aspartic acid.The peptide NCW might regulate kidney metabolic disorder of SHRs to alleviate hypertension by suppressing inflammation and improving nitric oxide production under the regulation of linoleic acid metabolism,folate related pathways,synthesis and degradation of ketone bodies,pyrimidine metabolism,β-alanine metabolism,and retinal metabolism.
基金supported by a grant from National Natural Science Foundation of China (82272196)。
文摘BACKGROUND:This study aims to explore whether Xuebijing(XBJ) can improve intestinal microcirculation dysfunction in sepsis and its mechanism.METHODS:A rat model of sepsis was established by cecal ligation and puncture(CLP).A total of 30 male SD rats were divided into four groups:sham group,CLP group,XBJ + axitinib group,and XBJ group.XBJ was intraperitoneally injected 2 h before CLP.Hemodynamic data(blood pressure and heart rate) were recorded.The intestinal microcirculation data of the rats were analyzed via microcirculation imaging.Enzyme-linked immunosorbent assay(ELISA) kits were used to detect the serum levels of interleukin-6(IL-6),C-reactive protein(CRP),and tumor necrosis factor-α(TNF-α) in the rats.Histological analysis and transmission electron microscopy were used to analyze the injury of small intestinal microvascular endothelial cells and small intestinal mucosa in rats.The expression of vascular endothelial growth factor A(VEGF-A),phosphoinositide 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),protein kinase B(Akt),and phosphorylated Akt(p-Akt) in the small intestine was analyzed via Western blotting.RESULTS:XBJ improved intestinal microcirculation dysfunction in septic rats,alleviated the injury of small intestinal microvascular endothelial cells and small intestinal mucosa,and reduced the systemic inflammatory response.Moreover,XBJ upregulated the expression of VEGF-A,p-PI3K/total PI3K,and p-Akt/total Akt in the rat small intestine.CONCLUSION:XBJ may improve intestinal microcirculation dysfunction in septic rats possibly through the VEGF-A/PI3K/Akt signaling pathway.
基金funded by grants from Egg Farmers of Canada,Global Egg Corp.,and Natural Sciences and Engineering Research Council of Canada(NSERC)。
文摘Ovotransferrin,an iron-binding glycoprotein,accounting for approximately 12%of egg white protein,is a member of transferrin fam ily.Our previous studies showed that ovotransferrin stimulates the proliferation and differentiation of osteoblasts,while inhibits osteoclastogenesis and resorption activity.The work aims to study the efficacy of orally administered ovotransferrin on the prevention of osteoporosis using ovariectomized(OVX)Sprague-Dawley rats.Oral administration of ovotransferrin showed no negative effect on body weight,food intake and organ weight.After 12-week treatment,feeding ovotransferrin at a dose of 1%(1 g ovotransferrin/100 g diet)prevented OVX-induced bone loss and maintained relatively high bone mineral density and integrated bone microarchitecture.The serum concentration of biomarkers indicating bone formation was increased in ovotransferrin administration groups,while the bone resorption biomarkers were decreased.Ovotransferrin feeding also decreased the production of serum cytokine TNF-αand IL-6,which are two stimulators for osteoclast differentiation.In addition to its direct regulatory role on bone turnover,ovotransferrin supplementation might benefit osteoporosis prevention by inhibiting adipogenesis,and regulating immune response.Our results suggested the potential application of ovotransferrin as a functional food ingredient on the prevention of osteoporosis.
文摘Objective To evaluate the antagonistic effects of N-acetylcysteine(NAC)on mitogen-activated protein kinases(MAPK)pathway activation,oxidative stress and inflammatory responses in rats with lung injury induced by fine particulate matter(PM2.5).Methods Forty eight male Wistar rats were randomly divided into six groups:blank control group(C1),water drip control group(C2),PM2.5 exposed group(P),low-dose NAC treated and PM2.5 exposed group(L),middle-dose NAC treated and PM2.5 exposed group(M),and high-dose NAC treated and PM2.5 exposed group(H).PM2.5 suspension(7.5 mg/kg)was administered tracheally once a week for four times.NAC of 125 mg/kg,250 mg/kg and 500 mg/kg was delivered intragastrically to L,M and H group respectively by gavage(10 ml/kg)for six days before PM2.5 exposure.The histopathological changes and human mucin 5 subtype AC(MUC5AC)content in lung tissue of rats were evaluated.We investigated IL-6 in serum and bronchoalveolar lavage fluid(BALF)by Enzyme-linked immunosorbent assay(ELISA),MUC5AC in lung tissue homogenate by ELISA,glutathione peroxidase(GSH-PX)in serum and BALF by spectrophotometry,and the expression of p-ERK1/2,p-JNK1/2 and p-p38 proteins by Western blot.All the measurements were analyzed and compared statistically.Results Lung tissue of rats exposed to PM2.5 showed histological destruction and increased mucus secretion of bronchial epithelial cells.Rats receiving NAC treatment showed less histological destruction and mucus secretion.Of P,L,M and H group,MUC5AC in lung tissue,IL-6 in serum and BALF were higher than controls(C1 and C2)(all P<0.05),with the highest levels found in the P group and a decreasing trend with increase of NAC dose.The activity of GSH-PX in serum and BALF of PM2.5 exposed rats(P,L,M and H)was lower than that of controls(all P<0.05),with higher activities found in NAC treated rats(L,M,and H),and an increasing trend with increase of NAC dose.The expressions of p-ERK1/2,p-JNK1/2 and p-p38 proteins in PM2.5 exposed lung tissue(P,L,M and H)was higher than controls(all P<0.05),with decreased levels and dose dependent downregulation found in NAC treated rats.Conclusion NAC can antagonize major MAPK pathway activation,lung oxidative stress and inflammatory injury induced by PM2.5 in rats.
文摘BACKGROUND： Paraquat （PQ） intoxication causes lung oxidative stress damage. Saturated hydrogen saline, a newly explored antioxidant, has been documented to play a powerful antioxidant role in preventing oxidative stress damage. This study aimed to investigate the protective effects and the possible mechanisms of intoxication on rats with acute lung injury （ALl） caused by paraquat poisoning. METHODS： Thirty PQ poisoned rats were randomly divided into a PQ intoxication group （intoxication group）, a saturated hydrogen saline intervention group （intervention group）, and a control group, with 10 rats in each group. The first two groups accepted an intragastric administration of PQ at a dose of 50 mg/kg for every single rat, and the control group was fed with a same volume of normal saline. Five mL/kg of saturated hydrogen saline was given to the intervention group three times a day by peritoneal injection for three days after intoxication. Arterial blood gas was detected on the third day. The rats were executed and their lungs were taken for measurement of wet dry weight ratio, homogenate malondialdehyde （MDA）, and 8-hydroxy-2＇-deoxyguanosine （8-OhdG）. Histological changes of the lungs were also observed. RESULTS： Compared with the control group, the intoxication group had more serious hypoxemia, greater wet/dry weight ratio, higher MDA level, higher expression of 8-OhdG and more severe lung damage （P〈0.01 or P〈0.05）. However, after intervention with saturated hydrogen saline, poisoned animals turned to have lighter hypoxemia, smaller wet/dry weight ratio, lower MDA level, lower expression of 8-OhdG, and milder lung damage （P〈0.01 or P〈0.05）. CONCLUSIONS： Saturated hydrogen sal by PQ. Possibly, it can neutralize toxic oxygen injury induced by PQ. ne is effective in preventing acute lung injury caused radicals selectively and alleviate the oxidative stress
基金Supported by State Scientific Key Projects for New Drug Research and Development (2009ZX09102-250)High-tech Research Project for Medicine and Pharmacology of Jiangsu Province (BG20070605)
文摘Objective To assess the severity and reversibility of the chronic toxicity of a novel recombinant human granulocyte colony-stimulating factor (rhG-CSFa) in rats and the dose-effect relationship.Methods A total of 100 Sprague-Dawley rats (equal numbers of male and female) were randomly divided into five groups (20 rats in each group):four groups were treated with rhG-CSFa at 500,100,10,1 μg/kg,respectively,and one group was treated with vehicle only to serve as the control.The rats were received subcutaneous injections of rhG-CSFa or vehicle daily for 13 weeks.During the course of the chronic toxicity study,the physical status,body weight,and food consumption were monitored.Half of the rats in each group (n=10) were sacrificed after the last rhG-CSFa administration,and the other half were sacrificed at five weeks after the last rhG-CSFa administration.Urinalyses,blood biochemistry,hematological analysis,histopathological examination,and immunological tests were performed for each of the rats.Results The hematological analyses revealed that the mean white blood cells count,neutrophils count,and neutrophils percentage were increased in male rats at the dose of 10 μg/kg or higher,and these were related with the biological activity of rhG-CSFa.Some small abnormalities were observed in the spleen of a few rats when used highest dose (500 μg/kg,a dosage of 200 folds higher than the normal clinical dosage),but these abnormalities were recovered within 5-week recovery period.No other rhG-CSFa-related abnormalities were observed in this chronic toxicity study.Conclusion No significant toxicity and immunogenicity are observed with rhG-CSFa administration to rats in the chronic toxicity studies.
基金Fund supported by the Natural Science Foundation of Zhejiang Province (LQ12H27005).
文摘Objective To investigate the combined effects of chronic obstructive pulmonary disease(COPD)and depression on spatial memory in old rats,aiming to better understand the comorbidity of the two diseases in geriatric patients.Methods The SD rats were assigned into five groups:adult control group(n=6),elderly control group(n=6),elderly COPD group(n=6),elderly depression group(n=6)and elderly COPD with depression group(n=6).Smoking and chronic unpredictable mild stress(CUMS)with solitary support were used to induce COPD model,depression model,respectively,and the both were applied for the comorbidity model.Learning and memory deficits were assessed by Morris water maze(MWM)test.The activity of superoxide dismutase(SOD)and the content of malondialdehyde(MDA)in serum and hippocampus tissue were determined by Xanthinoxidase method and Thiobarbituric acid reaction(TBAR)method,respectively.Results The results of pulmonary histology,lung function,open-field test and sucrose consumption demonstrated the comorbidity models of COPD and depression in elderly rats were successfully established using smoking and CUMS with solitary support.Compared with the elderly control group,the group of COPD with depression had obviously longer time of latency and longer travel distance to reach the platform in MWM test(LSD-t=-10.116,P=0.000;LSD-t=-6.448,P=0.000).The SOD activity in serum and hippocampus decreased significantly(LSD-t=2.629,P=0.014;LSD-t=2.215,P=0.044)and the MDA content in serum and hippocampus increased significantly(LSD-t=-2.140,P=0.042;LSD-t=-2.070,P=0.049)in elderly COPD with depression group.Conclusions COPD in comorbidity of depression could induce spatial memory deficit in old rats.The mechanisms might be related to the overloaded and free radical metabolic imbalance.These results suggest a potential therapeutic target for comorbidity of COPD and depression in geriatric patients.
文摘Objective To investigate the antagonistic effects of different doses of Lianhua Qingwen on pulmonary injury induced by fine particulates PM2.5 in rats. Methods Fine particulates suspended in the environment were collected. Forty-eight healthy adult wistar rats were randomly divided into 6 groups with 8 rats in each group. Four groups of rats were exposed to PM2.5 by intratracheally dripping suspensions of fine particulates PM2.5(7.5 mg/kg) as dust-exposed model rats. Among them 24 rats in three groups received Lianhua Qingwen treatment(crude drug) at a dose of 2 g/kg, 4 g/kg, 8 g/kg per day for 3 days before dust exposure and were defined as low-dose, middle-dose and high-dose Lianhua Qingwen treatment groups respectively. The other dust-exposed model rats without treatment were assigned as PM2.5 control group. The un-exposed rats were set as saline control group(1.5 ml/kg saline) and blank control group. All rats were killed after 24 hours of the exposure. Lung tissue, serum and bronchoalveolar lavage fluid(BALF) were collected. The levels of malonaldehyde(MDA), lactate dehydrogenase(LDH), and glutathione peroxidase(GSH-PX) in blood serum and BALF, and superoxide dismutase(SOD) in blood surum were measured using fluorescent quantitation PCR; Expression of NF-E2-related factor 2(NRF-2), heme oxygenase 1(HO-1) and quinone oxidoreductase 1(NQO1) in lung tissues were measured using Western blot. Pathological changes of lung tissues in each group were also examined. Results Pathology revealed thickened alveolar septum, congestion of capillary, interstitial edema and infiltration of lymphocyte and neutrophil surrounding bronchiole in the PM2.5 control group, which weresignificantly relieved in the Lianhua Qingwen treatment groups. Compared to the blank and saline control groups, the PM2.5 control group had significantly higher levels of LDH and MDA(p<0.01) and lower level of GSH-PS(p<0.01) in BALF, significantly higher levels of LDH and MDA(p<0.05) and lower level of GSH-PS(p<0.05) in rat serum. The levels of MDA in blood serum and BALF were significantly lower in each treatment group than that in PM2.5 control group(all P<0.05). In both middle-dose and high-dose treatment group the measurements of LDH in serum and BALF as well as GSH-PX in serum were significant difference from those of PM2.5 control group(all P<0.05). Expressions of NRF-2, HO-1 and NQO1 in lung tissues were significantly different among middle-dose and high-dose treatment group compared with those in PM2.5 control group(all P<0.05). Conclusion Fine particulates PM2.5 in environment may induce pulmonary oxidative lesions in rats. Middle-dose and high-dose Lianhua Qingwen has antagonist effece on the injuries induced by fine particulates.
文摘This study was designed to establish an animal model of gastric mucosal precancerous lesions in Wistar rats and on this model, the mechanism to produce the precancerous lesions and their reverse therapy were studied. Ranitidine (R) 0.03% in the diet, N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)50 μg/ml in drinking water, or both of them were administered to Wistar rats for 20 weeks. The iats were maintained without the drugs for additional 23 weeks. A control group of rats without any treatment of drugs were kept for 43 weeks Intestinal metaplasia (IM) was found in 86.5% of the rats in MNNG group, 22.5% in R groupand 100% in MNNG+R while only 7.5% in the control. The incidence of IM was significantly different between MNNG+R group and R group or MNNG group. The number of metaplastic glands was also the highest in the MNNG+R group. The therapeutic effects of retinoic acid (RA) and sodium butyrate (SB) on the iNduced precancerousous lesions of the glandular gastric mucosa were observed. It was found that the incidence of IM, moderate and severe dysplasia, and gastric cancer and the number of metaplastic glands in the pylorus and fundus were significantly lower in RA treated group (72.0%, 24.0%, 0%, 130.2±93.9 and 51.5±39.1) and SB treated gioup (60.0%,20.0%, 0%, 70.3±46.8, and 39.8±29.6) than in the RA untreated group (100%, 52.2%, 16.0%, 442.4±230.0 and 247.4±112.07) and the SB untreated group (88.0%, 48.0%. 16.0%, 241.4±113.9 and 146.4±66.3)(P<0.01 to 0.05). A mucosal flap with vascular pedicle from the gastric wall of the Wistar rats was transplanted to the duodenum, jejunum and colon respectively and the rats were killed in the 3td, 6th, 9th and 12th month after operation. IM was found in all the gastric grafts to the intestines with optical and electron microscopy. It is concluded on the basis of the findings that the concomitant administration of MNNG and R is a reliable method to induce IM of gastric mucosa in rats; RA and SB are efficient agents for the reverse thevapy of the precancerous lesions of gastric glandular mucosa in rats; and the formation of IM of gastric mucosa might be a pH-related process. The possible mechanism of the development of IM was discussed.
基金SupportedbyNationalNaturalScienceFoundationofChina(No.39900078)the Research Foundation for Medical Science ofPLA(the9thFive-YearProgram)Foundation for Appli-cation and BasicResearchofChongqing
文摘Tumor necrosis factor(TNF) mRNA was determined with dot blotting in various viscera 24 h after severe burn injury in rats. It was found that TNF mRNA was detected in the liver, kidneys, spleen,lungs and small intestines in normal conditions. After burn in
文摘The effects of verapamil, a calcium antagonist, on arterial blood pressure and myocardial mitochondrial respiratory function were studied in rats after they were inflicted with 6 Gy irradiation and 30% TBSA full thickness burns. The preventive or therapeutic administration of verapamil exerted little effects on the arterial blood pressure but could effectively protect the myocardial mitochondrial respiratory function after combined radiation-burn injury in rats.The protective effects of verapamil might exercise through the reduction of calcium content in the mitochondria.
基金grants from China Medical Board in New York (98677)National Ministry of Education of China (01089)
文摘Objective To investigate the role of Caspase-3 in retinal damage caused by hght exposure in rats. Methods Light injury to retina was induced by persistent exposure to illumination （intensity ： 30 000 ± 50 lux） of operating microscope for 30 minutes in the right eyes of Sprague-Dawley rats. The pathological changes of retina were observed under optical and electron microscopies at different time points, which were 6 hours, 1,3,7, and 15 days after the hght exposure. Apoptosis of retinal cells was analyzed by flow cytometry. The activity of Caspase-3 was evaluated by using the Caspase-3 assay kit. At the same time, the expression of Caspase-3 protease was determined with Western blot analysis. Results The examination results of optical and transmission electron microscopes showed that edema of inner and outer segments of the retina, especially the chondriosome inside the inner segment, became obvious 6 hours after the light exposure. The change was deteriorated along with the increasing time. The structures of the discoidal valve dissociated in the outer segment simultaneously. Disorderly arranged nuclei, karyopycnosis, and thinning in the outer nuclear layer were observed. The retinal pigment epithelium almost disappeared during the later stage. The staining results of Annexin-V combined with PI demonstrated that the proportion of apoptotic cells increased with time. The proportion between 7th day （82.7%） and 15th day （80.4%）, however, showed no significant difference. Caspase-3 became remarkably active with the lapse of time, which increased from 0.02 at 6th hour to the peak of 9. 8 at 7th day before it started to descend. The Western blot detected a expression of the active form of Caspase-3 at 7th day and 15th day. Conclusion Apoptosis of photoreceptor cells is markedly involved in the light damage and Caspase-3 protease may play an important role in the apoptotic process of the retina after light exposure in rats.
文摘Immunoreactive substance P(Ir-SP)level,and substance P likeimmunoreactivity(SP-Li)in the spinal cord were observed with radioimmunoassay andimmunohistochemistry in rats after they were given an intraperitoneal injection of mor-phine(7.5mg/kg)or electroacupunctured(3V and 3Hz)on the “Jiaji point”.It wasfound that the pain threshold(PT),Ir-SP level and SP-Li in the dorsal horn of the spi-nal cord were more significantly increased in the animals after the administration ofmorphine or electroacupuncture than in the control(P【0.05～0.01).The combined effectsof morphine and electropacupuncture were even more powerful than either of the agentswas administered singly.Naloxone could block the analgesic effect and the elevation ofIr-SP due to morphine or electroacupuncture.The findings suggest that there is a synergismbe tween morphine and electroacupuncture and the analgesic effect of the 2 depends uponthe increase of Ir-SP level of the spinal cord mediated through the opiate receptors.
基金supported by a grant from the National Natural Science Foundation of China(81070122)
文摘BACKGROUND:Sepsis-induced myocardial injury is one of the major predictors of morbidity and mortality of sepsis.The cytoprotective function of erythropoietin(EPO) has been discovered and extensively studied.However,the cardioprotective effects of EPO on sepsis-induced myocardial injury in the rat sepsis model has not been reported.METHODS:The rat models of sepsis were produced by cecal ligation and perforation(CLP)surgery.Rats were randomly(random number) assigned to one of three groups(n=8 for each group):sham group,CLP group and EPO group(1000 lU/kg erythropoietin).Arterial blood was withdrawn at3,6,12,and 24 hours after CLP.cTnl,BNP,CK-MB,LDH,AST,TNF-a,IL-6,IL-10,and CRP were tested by the ELISA assay.Changes of hemodynamic parameters were recorded at 3,6,12,24 hours after the surgery.Histological diagnosis was made by hematoxylin and eosin.Flow cytometry was performed to examine cell apoptosis,myocardium mitochondrial inner membrane potential,and NF-κB(p65).Survival rate at 7 days after CLP was recorded.RESULTS:In the CLP group,myocardial enzyme index and inflammatory index increased at3,6,12 and 24 hours after CLP compared with the sham group,and EPO significantly blocked the increase.Compared with the CLP group,EPO significantly improved LVSP,LV +dpldt_(max) LV-dp/dt_(min),and decreased LVEDP at different time.EPO blocked the reduction of mitochondrial transmembrane potential,suppressed the cardiomyocyte apoptosis,inhibited the activation of NF-κB,and reduced the production of proinflmmatory cytokines.No difference in the survival rate at 7 days was observed between the CLP group and the EPO group.CONCLUSION:Exogenous EPO has cardioprotective effects on sepsis-induced myocardial injury.
文摘The effects of different ambient pressures of 53.99,61.33 and 96.60 kPa on theseverity of blast injury were observed in rats.It was found that when the incident shock wavewas 190.40 kPa in its peak pressure and 10 ms in its duration, both the mortality and the severityof lung injury were progressively increased along with the decrease of the ambient pressure.Themortality rate of the rats in the 6th hour after exposure was 0%,25% and 36.8% and the hem-orrhagic area on the lungs was 63.75+69.01,313.50+357.25 and 653.21+652.25 squaremilimeters when the ambient pressure was 96.60,61.33 and 53.99 kPa respectively.In addi-tion, the lung/body index was 0.93+0.21%,1.31+0.65% and 1.50+0.77% respectively.Itis believed that the decrease of the ambient pressure might decrease the tolerance of the rat to theimpact of blast waves to result in higher mortality and more extensive hemorrhage on the lungs.
文摘Objective To examine the effects of exogenously administered intermedin （IMD,adrenomedullin-2） on arterial blood pressure,cardiac function and the cardiovascular IMD receptor system in spontaneously hypertensive rats （SHRs） as well as to investigate the associated mechanisms.Methods Thirteen week-old male rats were divided in Wistar Kyoto （WKY） group （n =12）,SHR group （n =12）,IMD group （SHRs infused with IMD 1-47 500 ng/kg per hour,n =12）,and ADM group （SHRs infused with adrenomedullin 500 ng/kg per hour,n =12）.Results A two-week continuous administration of low dose IMD 1-47 via mini-osmotic pumps markedly reduced blood pressure,the maximal rates of increase and decrease of left-ventricle pressure development （LV ± dp/dtmax）,left ventricular systolic pressure and heart rate in SHRs.Furthermore,IMD also inhibited protein over-expression of cardiovascular IMD receptors,myocardial Receptor Activity-Modifying Proteins （RAMP1 and RAMP2）,aortic RAMP1,RAMP2,RAMP3,and calcitonin receptor-like receptor （CRLR）;suppressed up-regulation of aortic RAMP1,RAMP2,RAMP3 and CRLR gene expression; and markedly elevated the mRNA abundance of myocardial atrial natriuretic peptide （ANP） and myocardial brain natriuretic peptide （BNP）.Additionally,IMD 1-47 administration in SHRs increased aortic cAMP concentration and reduced myocardial cAMP concentration.Conclusion These findings support the speculation that IMD,as a cardiovascular active peptide,is involved in blood pressure reduction and cardiac function amelioration during hypertension.The mechanism underlying this effect may involve IMD binding of a receptor complex formed by RAMPs and CRLR,and consequential regulation of cAMP levels and other cardiovascular active factors,such as ANP and BNP.
文摘Objective: To establish a stable reduced-size hepatic transplantation model in rats. Methods: Liver transplantation was performed in accordance with Kamada techniques. Many modifications were made including: Surgical manipulative innovation, adjustment of pre-operative drug administration and removed liver volume. Results: Forty-two rats underwent reduced-size hepatic transplantation; of them 33(84.6%) survived more than 1 week. The causes of postoperative death were peritonitis, inferior vena cava thrombus and unknown complications. Conclusion: Manipulative innovation and proper drug administration can improve the survival rate of rats apparently. Grafts regeneration can be triggered by the removal of left lateral segment and caudate lobe.
基金the National Natural Science Foundation of China(81472961)the Natural Science Foundation of Zhejiang Province(LY13H150001)the Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents.
文摘BACKGROUND:This study aims to explore the characteristics of the epithelial-to-mesenchymal transition(EMT)process and its underlying molecular mechanisms in the period of paraquat(PQ)-induced pulmonary fi brosis(PF).METHODS:Picrosirius red staining and collagen volume fraction were utilized to evaluate the pathological changes of PQ-induced PF in rats.Immunohistochemistry,Western blot,and real-time reverse transcriptase-polymerase chain reaction(RT-PCR)were used to measure the protein and gene expression of EMT markers,EMT-associated transcription factors,and regulators of EMT-related pathways,respectively.RESULTS:The collagen deposition in the alveolar septum and increased PF markers were characteristics of pathological changes in PQ-induced PF,reached a peak on day 14 after PQ poisoning,and then decreased on day 21.The protein and gene expression of the fibrosis marker,EMT markers,transcription factors,and regulators of EMT-related signaling pathways signifi cantly increased at diff erent time points after PQ poisoning compared with corresponding controls(P<0.05),and most of them reached a peak on day 14,followed by a decrease on day 21.The gene expression of EMT markers was significantly correlated with PF markers,transcription factors,and regulators of EMT-related signaling pathways(P<0.05).The mRNA expression of transcription factors was signifi cantly correlated with that of TGF-β1 and Smad2(P<0.05 or P<0.01),instead of Wnt2 andβ-catenin(P>0.05).CONCLUSIONS:EMT process plays a role in the PQ-induced PF,in which most PF and EMT markers have a peak phenomenon,and its underlying molecular mechanisms might be determined by further studies.
文摘Objective: To establish a model for pregnancy-induced hypertension syndrome in rats. Methods: Adult female Wistar rats were randomized into non-pregnant control (NN), non-pregnant cold-stress control (NC), pregnant control (PN) and pregnant cold-stress (PC) groups. The rats of NN and PN groups were put under 25 ℃ and those of NC and PC groups under (4±2)℃ for 4 h every morning respectively in the whole experimental period. The blood pressure, urine protein, body weight, haematocrit, weight of the placenta and weight and length of the fetus were recorded and the histological changes of the placenta and the kidneys were also studied. Results: The blood pressure and urine protein of the rats of the NC and PC groups after 2 weeks of cold-stress were more significantly increased than the rats of the NN and PN groups. In addition, the weight of the placenta and the weight and length of the fetus were more significantly lower in the former than the latter. Obvious changes of anoxia and ischemia were observed in the tissues of the kidneys and every layer of the placenta. Conclusion: Our findings of hypertension syndrome induced with repeated cold-stress in pregnant rats can be applied to illustrate the pathogenesis of pregnancy-induced hypertension syndrome in human beings.
