目的 探讨新型抗心衰药物沙库巴曲缬沙坦钠片（Entresto）在预防多柔比星（DOX）抗肿瘤药物所致心脏毒性中的效果。 方法 雄性成年ICR小鼠随机分为3组（n = 8）：对照组、DOX组和DOX+Entresto组。采用超声波心动描记术测量小鼠的心脏功能。H9c2细胞在DOX（1 mmol/L）存在或不存在的情况下用Entresto（0 ~ 48 μmol/L）预处理24 h，然后评估细胞生存力、氧化应激、凋亡和线粒体功能。 结果 与对照组相比，DOX组心肌细胞内CK、CK-MB和LDH的漏出量显著增加（P < 0.01），并出现左心室收缩功能障碍，Entresto给药逆转了DOX组的这些变化。DOX+Entresto组心肌细胞中的ROS水平和凋亡细胞数目显著低于DOX组（P < 0.05）。与DOX组相比，Entresto+DOX组H9c2细胞中的ROS水平和凋亡细胞数目显著降低（P < 0.05），和线粒体膜电位显著增加（P < 0.05）。Entresto逆转了DOX对SIRT1/PGC-1α/MFN2信号通路的抑制作用。 结论 Entresto通过抑制ROS介导的氧化应激和凋亡来改善DOX诱导的心脏毒性，其机制可能与SIRT1/PGC-1α/MFN2信号转导通路有关。

Objective To explore the efficacy of a new anti?heart failure drug， Entresto， in the prevention of cardiotoxicity caused by doxorubicin （DOX）. Methods Male adult ICR mice were randomly divided into three groups （n = 8）： control group， DOX group and DOX plus Entresto group. Cardiac function of mice was measured by echocardiography. H9c2 cells were pretreated with Entresto （0 - 48 μmol/L） for 24 hours in the presence or absence of DOX （1 mmol/L）， and then cell viability， oxidative stress， apoptosis and mitochondrial function were evaluated. Results As compared with the control group， leakage of CK， CK?MB and LDH increased significantly in the DOX group （P < 0.01）， and left ventricular systolic dysfunction occurred. Entresto administration reversed these changes in the DOX group. The level of ROS and the number of apoptotic cells in cardiomyocytes in the DOX plus Entresto group were lower than those in the DOX group （P < 0.05）. As compared with the DOX group， the level of ROS and the number of apoptotic cells in H9c2 cells decreased significantly in the Entresto plus DOX group （P < 0.05）， and mitochondrial membrane potential increased significantly （P < 0.05）. Entresto reversed the inhibitory effect of DOX on SIRT1/PGC?1α/MFN2 signaling pathway. Conclusions Entresto improves DOX?induced cardiotoxicity by inhibiting ROS?mediated oxidative stress and apoptosis， and its mechanism may be related to SIRT1/PGC?1α/MFN2 signal transduction pathway.