Background Doxorubicin is a widely used cytotoxic chemotherapy agent for treating different malignancies.However,its use is associated with dose-dependent cardiotoxicity,causing irreversible myocardial damage and sign...Background Doxorubicin is a widely used cytotoxic chemotherapy agent for treating different malignancies.However,its use is associated with dose-dependent cardiotoxicity,causing irreversible myocardial damage and significantly reducing the patient's quality of life and survival.In this study,an animal model of doxorubicin-induced cardiomyopathy was used to investigate the pathogenesis of doxorubicin-induced myocardial injury.This study also investigated a possible treatment strategy for alleviating myocardial injury through resveratrol therapy in vitro.Methods Adult male C57BL/6J mice were randomly divided into a control group and a doxorubicin group.Body weight,echocardiography,surface electrocardiogram,and myocardial histomorphology were measured.The 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 interval.These abnormalities were associated with vacuolation and increased disorder in the mitochondria of cardiomyocytes,increased protein expression levels ofα-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 levels.Conclusion Doxorubicin toxicity leads to abnormal mitochondrial morphology and dysfunction in cardiomyocytes and induces apoptosis by interfering with mitochondrial fusion.Resveratrol ameliorates doxorubicin-induced cardiotoxicity by activating SIRT1/MFN2 to improve mitochondria function.展开更多
基金Tianjin Key Medical Discipline(Specialty)Construction Project,Grant/Award N umber:TJY XZDXK-029ANational Natural Science Foundation of China,Grant/Award Numbers:81970270,82170327Tianjin Postgr aduate Scientific Research Innovation Projec,G rant/Award Number:2021YJSB278。
文摘Background Doxorubicin is a widely used cytotoxic chemotherapy agent for treating different malignancies.However,its use is associated with dose-dependent cardiotoxicity,causing irreversible myocardial damage and significantly reducing the patient's quality of life and survival.In this study,an animal model of doxorubicin-induced cardiomyopathy was used to investigate the pathogenesis of doxorubicin-induced myocardial injury.This study also investigated a possible treatment strategy for alleviating myocardial injury through resveratrol therapy in vitro.Methods Adult male C57BL/6J mice were randomly divided into a control group and a doxorubicin group.Body weight,echocardiography,surface electrocardiogram,and myocardial histomorphology were measured.The 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 interval.These abnormalities were associated with vacuolation and increased disorder in the mitochondria of cardiomyocytes,increased protein expression levels ofα-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 levels.Conclusion Doxorubicin toxicity leads to abnormal mitochondrial morphology and dysfunction in cardiomyocytes and induces apoptosis by interfering with mitochondrial fusion.Resveratrol ameliorates doxorubicin-induced cardiotoxicity by activating SIRT1/MFN2 to improve mitochondria function.
