Relationship between mitofusin-2 and diabetes mellitus-caused influence on cardioprotection induced by sevoflurane postconditioning in rats

Objective To evaluate the relationship between mitofusin-2 (Mfn-2)expression and diabetes mellitus (DM)-caused influence on cardioprotection induced by sevoflurane postconditioning in rats. Methods Healthy male Sprague-Dawley rats, weighing 210-260 g, were studied.DM was induced by intraperitoneal 1% streptozotocin 60 mg/kg, and confirmed by blood glucose ≥16.7 mmol/L 72 h later.Thirty-six rats with DM were randomly divided into 3 groups (n=12 each) using a random number table: sham operation group (group DMS), myocardial ischemia-reperfusion group (group DMIR), and sevoflurane postconditioning group (group DMSP). Another 36 normal rats were selected, and were also randomly divided into 3 groups (n=12 each) using a random number table: sham operation group (group NS), myocardial ischemia-reperfusion group (group NIR), and sevoflurane postconditioning group (group NSP). Myocardial ischemia was induced by 30 min occlusion of the left anterior descending branch of the coronary artery, followed by 120 min reperfusion.In NSP and DMSP groups, sevoflurane was inhaled for 5 min after the end-tidal concentration reached 2.5% starting from 1 min before reperfusion.The rats were sacrificed at 120 min of reperfusion, and their hearts were removed for measurement of myocardial infarct size (IS) (by TTC), cell apoptosis and Mfn2 expression, and for examination of pathological changes (with light microscope) and ultra-structure (with electron microscope). Apoptosis index (AI) was calculated. Results Compared with group NS, the myocardial IS was significantly enlarged, AI was increased, and the expression of Mfn-2 was down-regulated in NIR and NSP groups (P 0.05). Compared with group NSP, the myocardial IS was significantly enlarged, AI was increased, and the expression of Mfn-2 was down-regulated in group DMSR (P<0.05). The pathological changes were significantly attenuated in group NSP compared with group NIR.No significant difference was found in pathological changes between group DMSP and group DMIR. Conclusion The mechanism by which DM abolishes cardioprotection induced by sevoflurane postconditioning may be related to inhibited up-regulation of Mfn-2 expression in rats. Key words: Diabetes mellitus; Anesthetics, inhalation; Ischemic postconditioning; Myocardial reperfusion injury; Fusion proteins, bcr-abl