Mechanism of Resveratrol on autophagy mediated by Mst1/Sirt3 signaling pathway in diabetic cardiomyo

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Objective: To observe the effects of Resveratrol on myocardial cell injury and Mst1/Sirt3 signaling pathway mediated autophagy in type 2 diabetic mice. Methods: The mice were allocated to normal control group, model group, Resveratrol group, and melbine group, with 10 mice per group. Resveratrol group and melbine group were treated with resveratrol and metformin, respectively. The NC and the model group were treated with equal volume of normal saline by gavage for 8 consecutive weeks. HE staining, transmission electron microscopy and immunofluorescence were used to observe the pathological morphology, ultrastructure and apoptosis levels of myocardial tissues. RT-qPCR method was used to detect the expression levels of apoptosis genes Bax and Bcl-2 in myocardial tissues, and Western-blot method was used to detect the expression levels of autophagy proteins (LC3 and p62), Mst1 and Sirt3 proteins in myocardial tissue; Results: Compared with the model group, Resveratrol can significantly reduce the body weight, blood glucose level and serum CK and LDH levels of db/db mice, and the difference is statistically significant (P<0.05 and P<0.01). Meanwhile, after Resveratrol treatment, myocardial inflammation score, apoptosis rate, Bax mRNA expression level and Bax/Bcl-2 ratio in myocardial tissue were significantly reduced, and Bcl-2 mRNA expression level was significantly increased, and the difference was statistically significant (P <0.01). In addition, compared with the model group, the expression level of p62 and p-Mst1 protein in the myocardial tissue of the Resveratrol group was significantly reduced, and the expression level of Sirt3 protein and the ratio of LC3II/LC3I were significantly increased, and the difference was statistically significant (P<0.01). Conclusion: Resveratrol promotes the autophagy level of cardiomyocytes by activating the Mst1/Sirt3 signaling pathway and inhibits cardiomyocyte apoptosis to play a protective role in diabetic cardiomyopathy.
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