Complication of Anesthesia
Effect of inhibition of GSK-3β activity on sevoflurane postconditioning-induced cardioprotection in diabetic rats
Duan Yinglei, Yang Wenqu, Han Chongfang, Luo Min, Wang Xiaopeng, He Jiandong, Wang Xiang, Shi Gaoxiang, Li Tianci
Published 2016-09-20
Cite as Chin J Anesthesiol, 2016,36(9): 1068-1071. DOI: 10.3760/cma.j.issn.0254-1416.2016.09.008
Abstract
ObjectiveTo investigate the effect of inhibition of glycogen synthase kinase-3 beta(GSK-3β)activity on sevoflurane postconditioning-induced cardioprotection in diabetic rats.
MethodsHealthy adult male Sprague-Dawley rats, weighing 250-300 g, in which diabetes mellitus was induced by intraperitoneal 1% streptozotocin 60 mg/kg combined with high-fat and high-sucrose diet and confirmed by blood glucose level >16.7 mmol/L.Forty rats with diabetes mellitus were divided into 5 groups(n=8 each)using a random number table: sham operation group(S group), ischemia-reperfusion(I/R)group, sevoflurane postconditioning group(SP group), GSK-3β inhibitor SB216763 group(SB group), and sevoflurane postconditioning plus SB216763 group(SS group). Myocardial ischemia was induced by 30 min occlusion of the left anterior descending branch of the coronary artery followed by 120 min reperfusion.The rats inhaled sevoflurane with the end-tidal concentration of 2.5% for 5 min starting from 1 min before reperfusion in group SP.SB216763 0.2 mg/kg was injected via the caudal vein at 1 min before reperfusion in group SB.In group SS, the rats inhaled sevoflurane with the end-tidal concentration of 2.5% for 5 min starting from 1 min before reperfusion, and SB216763 0.2 mg/kg was injected via the caudal vein at 1 min before reperfusion.At 120 min of reperfusion, blood samples were collected from the carotid artery for determination of serum creatine kinase-MB(CK-MB)activity and cardiac troponin I(cTnI) concentrations.Myocardial specimens were collected at 120 min of reperfusion for microscopic examination of the pathological changes and for determination of myocardial infarct size(by 2, 3, 5-triphenyltetrazolium chloride staining)and phosphorylated GSK-3β(p-GSK-3β)expression(by Western blot).
ResultsCompared with group S, the myocardial infarct size and serum CK-MB activity and cTnI concentration were significantly increased, and the expression of p-GSK-3β was significantly down-regulated in I/R, SP, SB and SS groups(P<0.05). Compared with group I/R, the myocardial infarct size and serum CK-MB activity and cTnI concentration were significantly decreased, and the expression of p-GSK-3β was significantly up-regulated in SB and SS groups(P<0.05), and no significant change was found in the parameters mentioned above in group SP(P>0.05). Compared with group SB, the myocardial infarct size and serum CK-MB activity and cTnI concentration were significantly decreased, and the expression of p-GSK-3β was significantly up-regulated in group SS(P<0.05). The pathological changes of myocardium were significantly attenuated in SB and SS groups as compared with group I/R and group SP.
ConclusionInhibition of GSK-3β activity can improve sevoflurane postconditioning-induced cardioprotection in diabetic rats.
Key words:
Anesthetics, inhalation; Diabetes mellitus; Glycogen synthase kinase 3; Myocardial reperfusion injury
Contributor Information
Duan Yinglei
Department of Anesthesiology, Shanxi Medical University, Taiyuan 030001, China
Yang Wenqu
Department of Anesthesiology, Shanxi Dayi Hospital Shanxi Academy of Medical Sciences, Taiyuan 030032, China
Han Chongfang
Department of Anesthesiology, Shanxi Dayi Hospital Shanxi Academy of Medical Sciences, Taiyuan 030032, China
Luo Min
Department of Anesthesiology, Shanxi Dayi Hospital Shanxi Academy of Medical Sciences, Taiyuan 030032, China
Wang Xiaopeng
Department of Anesthesiology, Shanxi Dayi Hospital Shanxi Academy of Medical Sciences, Taiyuan 030032, China
He Jiandong
Department of Anesthesiology, Shanxi Dayi Hospital Shanxi Academy of Medical Sciences, Taiyuan 030032, China
Wang Xiang
Department of Anesthesiology, Shanxi Dayi Hospital Shanxi Academy of Medical Sciences, Taiyuan 030032, China
Shi Gaoxiang
Department of Anesthesiology, Shanxi Medical University, Taiyuan 030001, China
Li Tianci
Department of Anesthesiology, Shanxi Medical University, Taiyuan 030001, China