Effect of adenovirus-mediated mitofusin-2 gene transfection on sevoflurane postconditioning-induced cardioprotection in diabetic rats

Objective To investigate the effect of adenovirus-mediated mitofusin-2 (Adv-Mfn2) gene transfection on sevoflurane postconditioning-induced cardioprotection in diabetic rats. Methods Healthy adult male Sprague-Dawley rats, weighing 210-260 g, aged 3-4 months, in which diabetes mellitus was induced by intraperitoneal streptozotocin 60 mg/kg and confirmed by blood glucose level >16.7 mmol/L, were used in this study.Fifty rats with diabetes mellitus were randomly divided into 5 groups (n=10 each) using a random number table: sham operation group (S group), ischemia-reperfusion (I/R) group, sevoflurane postconditioning group (SP group), Adv-Mfn2 plus I/R group (M+ I/R group), and Adv-Mfn2 plus sevoflurane postconditioning group (M+ SP group). Myocardial ischemia was induced by 30 min occlusion of the left anterior descending branch of the coronary artery followed by 120 min reperfusion.In SP and M+ SP groups, sevoflurane was inhaled for 5 min with the end-tidal concentration of 2.5% starting from 1 min before reperfusion.Adv-Mfn2 2×1010 pfu/kg was injected via the sublingual vein at 1 min after streptozotocin injection in M+ I/R group and M+ SP group.The blood samples were collected from the abdominal artery at 120 min of reperfusion for determination of the creatine kinase-MB (CK-MB) activity and cardiac troponin I (cTnI) concentration in serum.The rats were then sacrificed, and their hearts were removed.Myocardial specimens were obtained for determination of cell apoptosis, and the apoptosis index (AI) was calculated.Myocardial specimens were obtained from the apex for determination of Mfn2 expression (by Western blot) and for examination of the pathological changes which were scored. Results Compared with S group, the CK-MB activity and cTnI concentration in serum, AI and pathological scores were significantly increased, and Mfn2 expression was significantly down-regulated in I/R, SP, M+ I/R and M+ SP groups (P 0.05). Compared with SP group, the CK-MB activity and cTnI concentration in serum, AI and pathological scores were significantly decreased, and Mfn2 expression was significantly up-regulated in M+ I/R and M+ SP groups (P<0.05). Compared with M+ I/R group, the CK-MB activity and cTnI concentration in serum, AI and pathological scores were significantly decreased, and Mfn2 expression was significantly up-regulated in M+ SP group (P<0.05). Conclusion Adv-Mfn2 gene transfection can improve sevoflurane postconditioning-induced cardioprotection in diabetic rats. Key words: Membrane fusion proteins; Transfection; Anesthetics, inhalation; Ischemic postconditioning; Diabetes mellitus; Myocardial reperfusion injury