Dihydromyricetin Prevents Diabetic Cardiomyopathy via miR-34a Suppression by Activating Autophagy

Purpose The pro-aging miRNA, miR-34a, is hyperactivated in the cardiac myocardial tissues ofpatients and mice with diabetes, leading to diabetic cardiomyopathy (DCM). Increasing evidence suggests that dihydromyricetin (DHM) can be used to effec- tively treat cardiomyopathy. In this study, we investigated whether DHM affects the expression ofmiR-34a in DCM. Methods The expression of miR-34a in high-glucose-induced cardiomyocytes and in the heart tissue of diabetic mice was determined by microRNA isolation and quantitative reverse transcription-polymerase chain reaction. Lipofectamine 3000 was used to transfect cardiomyocytes with miR-34a inhibitor, miR-34a mimics, and miR-control. These agents were intravenously injected into the tail vein of streptozotocin-induced diabetic mice. Autophagy and apoptosis were assessed in high-glucose- induced cardiomyocytes and cardiac tissue in diabetic mice by western blotting, immunofluorescence, Masson staining, hema- toxylin and eosin staining (H&E), and electron microscopy. Results DHM clearly ameliorated the cardiac dysfunction in the diabetic mice. The expression ofmiR-34a was up-regulated in high-glucose-induced cardiomyocytes and in the hearts of diabetic mice, thus impairing autophagy. Treatment with DHM decreased the expression of miR-34a and rescued the impairment of autophagy in high-glucose-induced cardiomyocytes and in the heart tissue ofdiabetic mice, while the miR-34a mimic offset the effect ofDHMwith respect to the development ofDCM by inhibiting autophagy. Conclusions By decreasing the expression of miR-34a, DHM restores impaired autophagy, and thus ameliorates DCM. Therefore, DHM may potentially be used in the treatment ofDCM.