松果菊苷对多柔比星心脏毒性保护作用及机制研究

Study on the Protective Effect and Mechanism of Echinacoside on Doxorubicin-induced Cardiotoxicity

目的:观察松果菊苷(ECH)能否减轻多柔比星(DOX)心脏毒性并初步阐明其作用机制。方法:通过单次腹腔注射大剂量多柔比星(15 mg/kg)建立急性心脏毒性小鼠模型,DOX处理后每日通过腹腔注射ECH(50 mg/kg/day)。实验分组如下:正常组(Control组);单纯松果菊苷处理组(ECH组);多柔比星处理组(DOX组);多柔比星+松果菊苷处理组(DOX+ECH组)。给药5天后检测左心室功能、心肌组织病理改变、氧化应激和心肌凋亡情况。结果:与Control组相比,DOX组小鼠心脏收缩和舒张功能明显减弱,心肌细胞出现空泡变性,心肌MDA含量、凋亡率以及促凋亡蛋白Bax和cleaved Caspase-3表达明显增加,而抑制凋亡蛋白Bcl-2表达量、SOD与GSH-Px活性明显下降。与DOX组相比,松果菊苷能明显改善心脏功能,缓解心肌空泡变性,降低MDA含量、凋亡率以及Bax和cleaved Caspase-3表达量,而提高Bcl-2表达量、SOD与GSH-Px活性(均P <0.05)。结论:松果菊苷可以通过抑制心肌组织氧化应激损伤和凋亡缓解多柔比星诱导的急性心脏毒性。

Objective: To observe whether echinacoside(ECH) can alleviate doxorubicin(DOX)-induced cardiotoxicity and preliminarily elucidate its mechanism of action. Methods: A mouse model of acute cardiotoxicity was established by a single intraperitoneal injection of high-dose doxorubicin(15 mg/kg). ECH(50 mg/kg/day) was injected intraperitoneally daily after DOX treatment. The experimental groups were as follows: Control group;ECH group;DOX group;and DOX+ECH group. Left ventricular function, myocardial histopathological changes, oxidative stress and myocardial apoptosis were determined 5 days after DOX administration. Results: Compared with the Control group, the systolic and diastolic function was significantly impaired, the vacuolar degeneration of the cardiomyocytes was observed, the MDA content, apoptosis ratio and the expression levels of the proapoptotic proteins Bax and cleaved Caspase-3 were significantly increased, and the expression level of anti-apoptotic protein Bcl-2, and the activities of SOD and GSH-Px were significantly decreased in the DOX group. Compared with the DOX group, echinacoside significantly improved cardiac function, ameliorated myocardial vacuolar degeneration, reduced MDA content, apoptosis ratio and Bax and cleaved Caspase-3 expression, and increased Bcl-2 expression, SOD and GSH-Px activities(all P < 0.05). Conclusion: Echinacoside could alleviate the acute cardiotoxicity induced by DOX by inhibiting myocardial oxidative stress damage and apoptosis.