糖尿病心肌病（DBCM）引起的心力衰竭（心衰）是糖尿病致死、致残的主要原因。已知自噬是其致病机制之一，但是，氧连-N-乙酰葡萄糖胺修饰(O-GlcNAc)和其底物蛋白SNAP29如何调控自噬在DBCM心衰发生中的机制作用未见报道。我们前期研究发现，在I型DBCM大鼠中，SNAP29-O-GlcNAc修饰水平明显增高；给予糖基化激动剂时，DBCM鼠心脏功能下降；而降低糖基化水平，心脏功能改善。鉴于SNAP29蛋白可能参与自噬过程膜的形成，故提出假设：SNAP29-O-GlcNAc修饰通过调控自噬影响DBCM心衰的进展。为验证假说，本研究从细胞到动物模型水平，结合糖基化修饰及自噬相关抑制剂、激动剂等，探索SNAP29-O-GlcNAc修饰对自噬，及自噬在O-GlcNAc-SNAP29调控的DBCM心衰进展中具体的作用机制。为临床寻找DBCM治疗靶点提供实验基础。

Heart failure caused by diabetic cardiomyopathy (DBCM) is the main cause of mortality in diabetes. Autophagy is one of its pathogenic mechanisms, while, there is still no report on how O-GlcNAc and its substrate protein SNAP29 regulates the pathogenesis of DBCM via autophagy. Our preliminary results showed that the level of SNAP29 O-GlcNAc modification was significantly increased in the heart of type I diabetes rat, what was more interesting, overexpression of O-GlNAc modified SNAP29 aggravated cardiac function, and inhibition of SNAP29 O-GlcNAc modification protected heart from DBCM. Since SNAP29 is involved in autophagy membrane formation, thus we propose a hypothesis that autophagy modulated by SNAP29 O-GlcNAc affects the progress of DBCM related heart failure. We will apply both O-GlcNAc and autophagy agonist and inhibitor to verify the mechanism in vivo and in vitro,and the results will provide an experimental basis for clinical search of DBCM related heart failure.