Role of autophagy in Parkin over-expression-induced reduction of cardiac hypertrophy in diabetic rats / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the role of autophagy in Parkin over-expression-induced reduction of cardiac hypertrophy in diabetic rats.Methods Thirty-two healthy SPF male Sprague-Dawley rats,aged 2 months,weighing 200-230 g,were divided into 4 groups (n =8 each) using a random number table method:non-diabetes mellitus (DM) group (group Non-DM),DM group,DM plus AAV9-CMV-Parkin group (group DM+P) and DM puls AAV9-CMV-Parkin puls autophagy inhibitor 3-methyladenine (3-MA) group (group DM+P+MA).DM was induced by intraperitoneal streptozotocin (STZ) 60 mg/kg and confirmed by blood glucose level ＞16.7 mmol/L,and Parkin overexpression was achieved with adeno-associated virus serotype 9 as a vector.AAV9-CMV-Parkin 1 × 1012 mg/kg was injected into the tail vein at 3 weeks after STZ injection in group DM+P.In group DM+P+MA,AAV9-CMV-Parkin 1× 1012 mg/kg was injected into the tail vein at 3 weeks after STZ injection,and 3 weeks later 3-MA 15 mg/kg was injected into the tail vein,once a week for 6 weeks in total.Cardiac diastolic and systolic function was detected using Bmode ultrasonography.Cardiomyocytes were obtained for microscopic examination of the cross-sectional area (with a light microscope) and for determination of the expression of microtubule-associated protein 1 light chain 3,P62 and Parkin.Results Compared with group Non-DM,the cross-sectional area of cardiomyocytes was significantly increased,and the diastolic and systolic function was decreased in DM group (P＜0.05).Compared with group DM,the cross-sectional area of cardiomyocytes was significantly decreased,the diastolic and systolic function was improved,the expression of microtubule-associated protein 1 light chain 3 and Parkin in myocardial tissues was up-regulated,and the expression of P62 was down-regulated in group DM+P (P＜0.05).Compared with group MD+P,the cross-sectional area of cardiomyocytes was significantly increased,the diastolic and systolic function was decreased,the expression of microtubule-associated protein 1 light chain 3 was down-regulated,and the expression of P62 was up-regulated in group DM+P+MA (P＜0.05) Conclusion Autophagy is involved in Parkin over-expression-induced reduction of cardiac hypertrophy in diabetic rats.