Muscone alleviates myocardial ischemia-reperfusion injury via inhibition of oxidative stress and enhancement of SIRT3.

Abstract

This study aimed at probing into the function of muscone in ameliorating myocardial ischemiareperfusion (I/R) injury and exploring the underlying mechanism. To analyze the function of muscone, H9c2 cardiomyocytes were treated with hypoxia/reoxygenation (H/R) and Sprague-Dawley (SD) rats were treated with left anterior descending (LAD) of the coronary artery ligation for 30 min and reperfusion for 2 h to induce myocardial I/R injury. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect the expression of SIRT3. MTT assay and TUNEL assay were performed to investigate H9c2 viability and apoptosis, respectively. ELISA was employed to determine the expressions of inflammatory cytokines TNF-α, IL-6 and IL-1β, and myocardial injury markers CK and LDH. Oxidative stress markers MDA and SOD, and ROS expression levels were also detected. SIRT3 inhibitor 3-TYP was used to further confirm whether muscone worked via the augmentation of SIRT3. Herein, we found that muscone significantly inhibited inflammation and oxidative stress in H9c2 cardiomyocytes in a dose-dependent manner. H9c2 viability was promoted by muscone while apoptosis was inhibited. In SD rats, pre-treatment of muscone alleviated I/R injury-induced cardiac function dysregulation and left ventricle remolding. Furthermore, muscone increased SIRT3 expression at both mRNA and protein levels. With 3-TYP inhibiting SIRT3, the protective effects of muscone in H9c2 cardiomyocytes and SD rats were all significantly alleviated. In summary, muscone can attenuate inflammation, oxidative stress and cardiomyocytes injury in H9c2 cells treated with H/R and alleviate myocardial I/R injury of SD rats, which are dependent on SIRT3.