The Role Of Sufentanil Postconditioning In Myocardial Ischemia-reperfusion Injury In Diabetic And Non-diabetic Rats And With The PI3K-AKT Signal Pathway And MPTP

Objective:To investigate the role of sufentanil postconditioning in myocardial ischemia-reperfusion injury in diabetic and non-diabetic rats and with the PI3K-AKT signal pathway and m PTP.Methods:Healthy male SD rats weighing 160-180 g were used in this study, which are provided by Shanxi Medical University. Diabetes mellitus was established by intraperitoneal streptozotocin 35 mg/kg and was confirmed by blood glucose≥16.7mmol/L. Two weeks after diabetes mellitus was induced, 24 rats were randomly divided into 4 groups(n=6 each): diabetic mellitus sham operation group(group DM-S), diabetic mellitus ischemia-reperfusion group(group DM-IR), diabetic mellitus sufentanil postconditioning group(group DM-SP) and diabetic mellitus sufentanil postconditioning+Wortmannin group(group DM-SP+W). Another 30 nondiabetic mellitus rats were also randomly divided into 4 group(n=6 each):nondiabetic mellitus sham operation group(group NDM-S), nondiabetic mellitus ischemia-reperfusion group(group NDM-IR), nondiabetic mellitus sufentanil postconditioning group(group NDM-SP) and nondiabetic mellitus sufentanil postconditioning+Wortmannin group(group NDM-SP+W). Myocardial ischemia-reperfusion was induced by 30 min occlusion of left anterior descending branch of coronary artery followed by 120 min reperfusion. Group S only thread ligation.Sufentanil postconditioning was induced by iv injection of sufentanil 3.0 μg/kg at 5 min before reperfusion. Group SP+W was induced by iv injection of Wortmannin(P13K inhibitor) 15 ug/kg before sufentanil. Arterial blood samples were collected at 120 min of reperfusion for measurement of plasma lactate dehydrogenase(LDH) activities and creatine kinase isoenzyme(CK-MB) concentration. At 120 min of reperfusion, the hearts were immediately removed for measurement of myocardial NAD+content by spectrophotometry at 440 nm and measurement of myocardial apoptosis by TUNEL and apoptosis index(AI) was calculated and myocardial infarction rang was calculated. The expression of Akt and phosphorylated Akt(p-Akt) was determined by Western blotting.Results:Compared with group S, LDH activities and CK-MB concentration and cardiomyocyte apoptosis index increased, NAD+content decreased and p-Akt/Akt up-regulated during myocardial ischemia reperfusion in group IR and group SP and group SP+W of diabetic and nondiabetic rats(p<0.05).Compared with group NDM-IR,LDH activities and CK-MB concentration and cardiomyocyte apoptosis index decreased,NAD+content increased and p-Akt/Akt up-regulated(p<0.05).Compared with group DM-SP, LDH activities and CK-MB concentration and cardiomyocyte apoptosis index increased, NAD+ content decreased and p-Akt/Akt up-regulated during myocardial ischemia reperfusion in group NDM-SP(p<0.05).Conclusion:Sufentanil postconditioning may attenuate cardiomyocyte apoptosis by IR injury in nondiabetic rat hearts through activating PI3K/Akt. Diabetes mellitus factor can negate sufentanil postconditioning induced protection against myocardial ischemia-reperfusion injury in rats.