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Resveratrol activation of SIRT1/MFN2 can improve mitochondria function,alleviating doxorubicin-induced myocardial injury

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Cancer Innovation 2023年第4期2卷 253-264页

作者： Qingling Zhang Yunpeng Zhang Bingxin Xie Daiqi Liu Yueying Wang Zandong Zhou Yue Zhang Emma King Gary Tse Tong Liu Department of Cardiology Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular DiseaseTianjin Institute of CardiologyThe Second Hospital of Tianjin Medical UniversityTianjinChina Epidemiology Research Unit Cardiovascular Analytics GroupChina-UK CollaborationHong KongChina Kent and Medway Medical School CanterburyKentUK

Background doxorubicin is a widely used cytotoxic chemotherapy agent for treating different ***,its use is associated with dose-dependent cardiotoxicity,causing irreversible myocardial damage and significantly reducing the patient's quality of life and *** this study,an animal model of doxorubicin-induced cardiomyopathy was used to investigate the pathogenesis of doxorubicin-induced myocardial *** study also investigated a possible treatment strategy for alleviating myocardial injury through resveratrol therapy in *** Adult male C57BL/6J mice were randomly divided into a control group and a doxorubicin *** weight,echocardiography,surface electrocardiogram,and myocardial histomorphology were *** mechanisms of doxorubicin cardiotoxicity in H9c2 cell lines were explored by comparing three groups(phosphate-buffered saline,doxorubicin,and doxorubicin with resveratrol).Results Compared to the control group,the doxorubicin group showed a lower body weight and higher systolic arterial pressure,associated with reduced left ventricular ejection fraction and left ventricular fractional shortening,prolonged PR interval,and QT *** abnormalities were associated with vacuolation and increased disorder in the mitochondria of cardiomyocytes,increased protein expression levels of α-smooth muscle actin and caspase 3,and reduced protein expression levels of Mitofusin2(MFN2)and Sirtuin1(SIRT1).Compared to the doxorubicin group,doxorubicin+resveratrol treatment reduced caspase 3 and manganese superoxide dismutase,and increased MFN2 and SIRT1 expression *** doxorubicin toxicity leads to abnormal mitochondrial morphology and dysfunction in cardiomyocytes and induces apoptosis by interfering with mitochondrial *** ameliorates doxorubicin-induced cardiotoxicity by activating SIRT1/MFN2 to improve mitochondria function.

关键词： cardio-oncology doxorubicin-induced cardiomyopathy mitochondriafunction resveratrol SIRT1 agonists

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