| Object: To evaluate the protective effect of resveratrol preconditioning on myocardial ischemia-reperfusion injury in diabetic rats,and to explore the protective effect of Nrf2/ARE signaling pathway in resveratrol preconditioning on myocardial ischemia-reperfusion injury in diabetic rats.Methods:Healthy adult male SD rats weighing 200-220 g and aged from 4 to 5 months were fed with high-fat diet for 4 weeks and then injected with streptozotocin 30mg/kg into abdominal cavity at one time to establish diabetic rat model.Thirty rats were randomly divided into three groups(n=10): sham operation group(Sham group),myocardial ischemia reperfusion group(MI/R group)and myocardial ischemia reperfusion + resveratrol group(MI/R + Res group).Rat models of myocardial ischemia-reperfusion injury were established by ligating left anterior descending coronary artery for 30 minutes and restoring perfusion for 120 minutes.In MI/R+Res group,15 mg/kg resveratrol was injected intraperitoneally 7 days before the establishment of myocardial ischemia-reperfusion injury model,once a day for 7 consecutive days.Sham group and MI/R group were intraperitoneally injected with a mixture of DMSO and PBS of equal volume.Left ventricular ejection fraction(LVEF)and left ventricular short axis shortening rate(FS)were measured by B-mode ultrasonography.Five rats were sacrificed 120 minutes after reperfusion.Myocardial infarction area was measured by TTC staining.Another five rats were sacrificed.The concentration of lactate dehydrogenase(LDH)and creatine kinase isoenzyme(CK-MB)were measured by abdominal aorta.Myocardial tissue was taken and heart was detected by ELISA.The contents of superoxide dismutase(SOD),malondialdehyde(MDA)and reactive oxygen species(ROS)in myocardium were measured by HE staining.The contents of Nrf2 in myocardium were observed by immunohistochemistry.The contents of Nrf2,nuclear factor-erythroid 2-related factor 2(n-Nrf2)and heme oxygenase-1(heme oxygenase-l-1)in myocardium were determined by Western blot.The expression of HO-1.Results:Compared with Sham,the concentration of LDH and CK-MB,ROS and MDA in MI/R and MI/R+Res groups increased significantly,the activity of LVEF and FS,SOD decreased significantly,the area of myocardial infarction increased,the expression of Nrf2,n-Nrf2 and HO-1 protein decreased(all P < 0.05);compared with MI/R+Res group,the concentration of LDH and CK-MB,ROS and MDA decreased significantly,the activity of LVEF and FS,SOD increased significantly.The area of myocardial infarction decreased and the expression of Nrf2,n-Nrf2 and HO-1 protein increased(all P < 0.05).Conclusion: This study confirms that resveratrol preconditioning can alleviate myocardial ischemia-reperfusion injury in diabetic rats.Nrf2/ARE signaling pathway is involved in the protective mechanism of resveratrol preconditioning on myocardium of diabetic rats. |
PDF Full Text Request