传统中药芪苈强心治疗阿霉素心肌病的分子机制研究

Doxorubicin-induced cardiomyopathy is a common complication of cancer chemotherapy, greatly threatening human health. However, effective methods for the prevention and treatment of Doxorubicin-induced cardiomyopathy are still lacking. Our recent large-scale clinical trial has demonstrated that traditional Chinese medication Qiliqiangxin could ameliorate the symptoms of patients with chronic heart failure. Our animal study also found that Qiliqiangxin could attenuate adverse ventricular remodeling after acute myocardial infarction. However, the effects of Qiliqiangxin in doxorubicin-induced cardiomyopathy remains elusive. .Our preliminary data indicated that Qiliqiangxin could improve cardiac functions of doxorubicin-induced cardiomyopathy mice and regulate the expression of autophagy-related mRNAs and proteins. Based on in vitro and in vivo experiments, this project will determine if Qiliqiangxin could treat doxorubicin-induced cardiomyopathy through promoting the autophagic flux. This study would help eatablish a novel promising therapeutic target of doxorubicin-induced cardiomyopathy and provide more theoretical and experimental evidence for the introducion of traditional Chinese medication to the whole world.

阿霉素所致心肌病是临床上肿瘤患者化疗后常见的一种并发症，严重危害人类健康，目前缺乏有效的防治方法。我们前期的一项大型临床试验证实芪苈强心可以改善慢性心力衰竭患者的症状，基础研究也证实芪苈强心可以防治心肌梗死后的重构不良。但是，芪苈强心是否可以防治阿霉素所致心肌病尚不清楚，更勿及其分子机制。我们的前期研究初步发现，芪苈强心可以保护阿霉素所致心肌病小鼠的心功能，且可以影响自噬相关基因及蛋白的表达。本项目拟基于细胞和动物整体水平的实验，明确芪苈强心是否可以防治阿霉素所致心肌病，以及该保护效应是否依赖于对于自噬流的疏通。基于本项目，将有望发掘出芪苈强心治疗阿霉素心肌病的靶点，为传统中药走向世界提供更多的理论和实验证据。

阿霉素所致心肌病是临床上肿瘤患者化疗后常见的一种并发症，目前缺乏有效的防治方法。我们前期的一项大型临床试验证实芪苈强心可以改善慢性心力衰竭患者的症状，基础研究也证实芪苈强心可以防治心肌梗死后的重构不良。但是，芪苈强心是否可以防治阿霉素所致心肌病及其生物学机制尚不清楚。本项目基于细胞和动物整体水平的实验，重点研究了芪苈强心是否可以防治阿霉素所致心肌病，以及该保护效应是否依赖于对于自噬流的疏通。首先，我们发现在动物水平上芪苈强心可以减轻阿霉素诱导的小鼠心脏损伤，并且通过体内水平检测自噬在小鼠阿霉素心肌病中的变化，明确了芪苈强心防治阿霉素所致心肌病参与调节了自噬过程。另外，我们还发现芪苈强心可通过上调PPARγ及PGC1-α改善由苯肾上腺素诱导的病理性心肌肥厚。基于本项目，将有望发掘出芪苈强心治疗阿霉素心肌病和病理性心肌肥厚的靶点，为传统中药走向世界提供更多的理论和实验证据。