扩张性心肌病是一种高发病率、高死亡率的心血管疾病，发病机制复杂。最新研究表明RBM20作为一种横纹肌中高度表达的基因，通过选择性剪接肌联蛋白，在扩张性心肌病发生、发展过程中起关键作用。项目组前期研究结果发现RBM20基因敲除小鼠心脏组织中自噬特异性标记物Beclin-1，LC3BⅡ，Atg7等表达上调，心肌细胞整体自噬水平发生明显变化。然而，RBM20基因如何通过调控自噬实现保护作用及相关分子机制目前尚不清楚。本课题拟在既往工作基础上，应用RBM20基因敲除及过表达小鼠模型，以GSK3β/ULK1等自噬信号通路为突破点，深入研究RBM20基因与心肌自噬通路主要蛋白变化及扩张性心肌病发生、发展过程的相关性，揭示RBM20基因发挥保护作用的可能分子机制；同时利用临床资源，验证动物实验中取得的结果，为RBM20基因作为扩张性心肌病的治疗新靶点提供理论依据，具有重要的理论意义和应用价值。

Dilated cardiomyopathy (DCM) is one of the most common cardiovascular disease with high mortality and morbidity. The pathogenesis of DCM is not clear at present. Latest research showed that RNA binding motif protein-20（RBM20）, a mainly expressed gene in striated muscle, played an important role in the process of dilated cardiomyopathy via regulating titin splicing. Moreover, our research group found the presence of upregulation of Beclin-1，LC3BⅡ, Atg7 and other molecular markers of autophagy in RBM20 knockout mice, which indicated an obvious change of autophagy in cardiac myocytes. However, the underlying molecular mechanism of the protection effects of RBM20 in DCM has not been elucidated. Thus, the purpose of this project is to investigate the relationship among RBM20, dilated cardiomyopathy and autophagy, and to elucidate the roles of autophagy pathways as GSK3β/ULK1 et al in the protection effects of RBM20 in dilated cardiomyopathy, via using the RBM20 over-expressed and knock-out mice model. Furthermore, clincal samples will be obtained from DCM patients to verify the results found in animals. The aim of the present study is to reveal how RBM20 gene plays an important role in the protection against dilated cardiomyopathy and to reveal the possible underlying mechanism. The research will show the therapeutic promise for RBM20 as a possible target in the management of DCM, which is most important for the diagnosis and future therapy of dilated cardiomyopathy.