Effect Of Inhibiting GSK-3? Activity On Myocardial Protection Against Ischemia Reperfusion Induced By Sevoflurane Postprocessing In Diabetic Rats

Objective:To investigate the effect of inhibiting GSK-3? activity on myocardial protection against ischemia reperfusion induced by sevoflurane postprocessing in diabetic rats.Methods:Diabetic rat models were induced by single intraperitoneal injection of streptozotocin?STZ?combined with high glucose and high fat diet.Forty adult male Sprague-Dawley rats up to standard which weighing 250-300 g were selected and randomly divided into 5 groups?n=8 each?: sham operation group?group S?,ischemia reperfusion group?group I/R?,sevoflurane postprocessing group?group SP?,GSK-3?activity inhibitor SB216763 group?group SB?,Sevoflurane postprocessing combined SB216763 treatment group?group SS?.Myocardial ischemia reperfusion injury models were induced by 30 min occlusion of left anterior descending coronary artery?LAD?followed by 120 min reperfusion.And hemodynamic parameters in rats was monitored continuously,heart rate,systolic pressure and mean arterial pressure was recorded separately at time of 15 min before ischemia?T₀?,15 min after ischemia?T₁?,120 min after reperfusion?T₂?,then,rate pressure product?RPP?was calculated.Artery blood 2ml was extracted from the right common carotid artery and serum was preserved after centrifugation.4 rats of each group were sacrificed and cardiac tissues were obtained after 2,3,5-Triohenyltetrazolium chloride?TTC?staining.Myocardial infarct size was measured by TTC staining.The other 4 rats of each group were selected to observemyocardial pathological structure under optical microscope after hematoxylin-eosin staining.CK-MB was meteraged by immune suppression method.cTnI was meteraged by ELISA.GSK-3? was meteraged with western-blot.Results:The HR,MAP,RPP in group S were significantly decreased than those of the other groups at T₁ and T₂?P < 0.05?.The HR,MAP,RPP in group I/R were significantly increased in group SB and group SS at T₂?P < 0.05?.Compared with group S,CK-MB and cTnI were increased,p-GSK-3? were decreased in the other groups?P < 0.05?.Compared with group I/R,CK-MB and cTnI were increased,p-GSK-3? was decreased in group SB and SS?P < 0.05?.Compared with group SB,it was more obviously in group SS about these items?P < 0.05?.Conclusion:Diabetic factors can attenuate the protective effect of sevoflurane on diabetic rats with myocardial ischemia-reperfusion injury,the mechanism may be GSK-3?phosphorylation blocked,and inhibition of GSK-3? activity can phosphorylate and restore the myocardial protection effect.