药物性心肌病是继发性心肌病主要的一种，其中抗肿瘤药物Doxorubicin（DOX）所引发的心肌病常表现为扩张性心肌病的特征，若不加干预最终可导致致命性心力衰竭，限制了其临床应用。自噬通路由于其发挥清除受损害的细胞器以维持细胞自身稳态近年来备受关注。利用自噬-溶酶体通路的激活快速清除DOX损害的心肌细胞内细胞器实现对受损害的心肌细胞的保护是本课题的主旨，本课题创新之处在于从转录水平探讨自噬通路在DOX诱导的斑马鱼和小鼠心肌损害中的保护作用，重点探讨转录因子EB（TFEB）发挥的作用，尤其是慢性药物作用导致的心肌重构中，TFEB对细胞凋亡、纤维增生、心肌肥厚的干预作用；机制方面，首先阐明TFEB通过激活或者抑制了哪些自噬分子，并且想筛选出发挥主要作用的几种分子，进一步探究其功能；其次更深一步机制研究上想证实TFEB的保护作用是否是通过诱导溶酶体的表达，减少自噬小体的堆积来实现。

Drug-induced cardiomyopathy is a major secondary cardiomyopathy, in which anticancer drugs Doxorubicin (DOX) –induced cardiomyopathy is usually characterized as dilated cardiomyopathy, it could eventually lead to heart failure if not intervened, which limits its clinical application. Autophagy pathway is a hot topic in recent years for its function of clearing damaged organelles and maintaining the cellular homeostasis. This grant mainly investigates the function of autophagy pathway in DOX-induced cardiac injury from transcription level. The most important thing is to investigate the protective role of transcription factor EB (TFEB) in DOX-induced zebra fish and mice heart injury models, especially roles in heart reconstruction caused by chronic cardiac injury. We try to investigate the function of TFEB on cardiomyocyte apoptosis、 cardiac fibrosis and hypertrophy. For the mechanism investigation, the first thing is to clarify the autophagy molecules activated or inhibited by TFEB, furthermore, pick up the most important moleculars and investigate their function. Further investigation is to verify the hypothesis: function of TFEB is played by decreasing the autophagosome accumulation through inducing lysosome protein expression.