Effect Of Resveratrol Preconditioning On Cx43 In Myocardial Ischemia Reperfusion Injury In Diabetic Rats

Objective :Resveratrol(Res)ischemic preconditioning was performed on diabetic rats to evaluate its effect in myocardial ischemia reperfusion injury,and to explore the role and effect of connexin43(Cx43)in resveratrol preconditioning on myocardial ischemia reperfusion injury in diabetic rats.Methods :Clean healthy adult male SD rats aged from 4 to 5 months and weighed 200~220g.Diabetic rat model was prepared by feeding with high-fat diet for 4 weeks and then intraperitoneal injection one time of 30mg/kg 1% streptozotocin citric acid buffer according to body weight and then feeding with high-fat diet for 8 weeks.Thirty diabetic rats were randomly divided into 3 groups(n=10 each): the Sham operation group(Sham group),the myocardial ischemia reperfusion group(MIR group),and myocardial ischemia reperfusion+resveratrol group(MIR+Res group).Ten normal rats were selected as the myocardial ischemia reperfusion+resveratrol group(N+Res group).Rat models of myocardial ischemia reperfusion injury was prepared by ligating the left anterior descending coronary artery for 30 minutes and restoring perfusion for 120 minutes.In the MIR+Res and N+Res groups,15mg/kg of resveratrol diluted with dimethyl sulfoxide(DMSO)and phosphate buffer saline(PBS)was injected intraperitoneally 7 days before the establishment of ischemia reperfusion model,once a day for 7 consecutive days.Sham and MIR groups were injected with a mixture of DMSO and PBS of equal volume.Abdominal aortic blood was colleced and cardiac tissue was taken at 120 minutes of reperfusion.The serum lactate dehydrogenase(LDH)and creatine kinase isoenzyme(CK-MB)were measured by automatic blood biochemical analyzer.Serum tumor necrosis factor-?(TNF-?)and interleukin-6(IL-6)concentrations were detected by Enzyme-linked immunosorbent assay(ELISA).Determination of myocardial malondialdehyde(MDA)content by thiobarbituric acid method(TCA)and ELISA was used to detect reactive oxygen species(ROS)in myocardial tissue.Myocardial superoxide dismutase(SOD)content was determined by the xanthine oxidase method(XOD).Observe myocardial histopathological changes after HE staining.The contents and expression of Cx43 in myocardium were measured by immunohistochemistry(IHC)and determined by Western blot.Results :In the Sham group,the myocardial tissue was intact and the myofibrils were arranged neatly,there was almost no inflammatory cell infiltration,and the cytoplasm was rich in mitochondria.In the MIR group,myocardial tissue was structurally disordered,myofibrils were lysed,there were a large number of inflammatory cells infiltrated,and mitochondria were rare in the cytoplasm.In the MIR+Res and N+Res groups,the degree of cell edema and myocardial structural disorders were significantly reduced compared with the MIR group,and a small amount of inflammatory cell infiltration was seen.Among them,the pathological damage of N+Res group was lighter than that of MIR+Res group.Compared with the MIR group,the concentrations of CK-MB,LDH,TNF-?,IL-6 and other myocardial injury markers and inflammatory factors in the MIR + Res group were reduced,MDA and ROS levels were reduced,SOD levels were increased,and Cx43 expression was increased(all P <0.05).Conclusion:Resveratrol pretreatment can reduce myocardial ischemia reperfusion injury in diabetic rats,and its protective mechanism is maybe related to Cx43.