Relationship between GSK-3β and Drp-1 during diabetes mellitus-caused antagonization of cardioprotection induced by sevoflurane postconditioning in rats

Objective To investigate the relationship between glycoprotein synthase kinase-3 (GSK-3β) and mitochondrial cleavage protein (Drp-1) during diabetes mellitus-caused antagonization of cardioprotection induced by sevoflurane postconditioning in rats. Methods Clean-grade healthy male Sprague-Dawley rats, weighing 250-300 g, were used in this study.Diabetes mellitus was induced by high-fat and high-sucrose diet and intraperitoneal streptozotocin 30 g/kg.Forty rats with diabetes mellitus were divided into 5 groups (n=8 each) using a random number table method: ischemia-reperfusion (I/R) group, sevoflurane postconditioning group (SP group), sevoflurane postconditioning plus Drp1 inhibitor Mivi-1 group (SM group), sevoflurane postconditioning plus GSK-3β inhibitor SB216763 group (SB group) and sevoflurane postconditioning plus Mivi-1 plus SB216763 group (SMB group). Myocardial I/R was induced by 30 min occlusion of the left anterior descending branch of the coronary artery followed by 120 min reperfusion.The rats inhaled 2.5% sevoflurane for 10 min starting from 5 min before reperfusion in SP, SM, SB and SBM groups.Mivi-1 1.2 mg/kg was injected via the caudal vein at 15 min before reperfusion in group SM.SB216763 0.2 mg/kg was injected via the caudal vein at 5 min before reperfusion in group SB.Mivi-1 1.2 mg/kg and SB216763 0.2 mg/kg were injected via the caudal vein at 15 and 5 min before reperfusion, respectively, in group SMB.Blood samples were collected from the abdominal aorta at 120 min of reperfusion for determination of serum cardiac troponin I (cTnI) concentrations.The rats were sacrificed and myocardial specimens were obtained from the apex for determination of the cell apoptosis (by TUNEL) and expression of caspase-3 (by Western blot), and apoptotic index (AI) was calculated. Results Compared with group I/R, no significant change was found in caspase-3 expression, AI or serum cTnI concentrations (P>0.05), and the pathological changes of myocardium were comparable in group SP, and the expression of caspase-3 was significantly down-regulated, and AI and serum cTnI concentration were decreased (P<0.05), and the pathological changes of myocardium were significantly attenuated in SM, SB and SMB groups.Compared with group SP, the expression of caspase-3 was significantly down-regulated, AI and serum cTnI concentrations were decreased (P<0.05), and the pathological changes of myocardium were significantly attenuated in SM, SB and SMB groups.Compared with group SMB or group SB, the expression of caspase-3 was significantly down-regulated, AI and serum cTnI concentrations were decreased (P<0.05), and the pathological changes of myocardium were significantly attenuated in group SMB. Conclusion It is not a single regulatory relationship between GSK-3β and Drp-1 in the pathophysiological process of diabetes mellitus-caused antagonization of cardioprotection induced by sevoflurane postconditioning in rats. Key words: Myocardial reperfusion injury; Anesthetics, inhalation; Diabetes mellitus; Glycogen synthase kinase 3; Mitochondrial proteins; Postconditioning