糖尿病性心肌病（DCM）所致的心力衰竭是引起2型糖尿病患者死亡的主要原因。因此，阐明DCM发生机制并寻找有效治疗靶点，成为目前DCM防治研究的热点。E1A激活基因阻遏子（CREG）是定位于细胞内体-溶酶体系统的小分子糖蛋白。它能够参与细胞内稳态调控，对抗病理性细胞损伤。我们前期研究发现，CREG在正常心肌细胞中高表达，过表达CREG能够对抗缺血或炎症引起的心肌细胞损伤；而在DCM模型小鼠心肌中，CREG表达则显著降低，提示其可能是DCM发生的重要调控分子。因此，本研究选择CREG为靶向分子，通过心肌特异性敲除和过表达CREG的DCM小鼠模型和原代心肌细胞模型，从在体和细胞水平分别阐明CREG在DCM发生及防治中的作用；并尝试从溶酶体-自噬保护这一重要的细胞内稳态调控通路入手，通过蛋白质芯片技术，阐明CREG调控DCM的分子机制，为DCM防治提供新的理论依据和分子靶点。

Diabetic cardiomyopathy (DCM) causes overt heart failure, which is the most common cause of death in patients with type 2 diabetes mellitus. Thus clarifying underlying mechanism and exploring effective target for treatment of DCM has become a hot topic in this field. Cellular repressor of E1A stimulated gene (CREG) is a small molecular glycoprotein locating in endosome-lysosome system, which is involved in maintenance of cellular homeostasis and protecting cells from pathological damages. Our preliminary data showed that CREG was highly expressed in cardiomyocytes under physiological condition, and over-expression of CREG alleviated cardiomyocyte damages induced by ischemia or inflammation. In addition, in a mouse model of DCM, we observed significant reduction of CREG in myocardium, suggesting that CREG might be a key factor involved in regulating onset and development of DCM. Therefore, the aim of this study is to elucidate the role and underlying mechanism of CREG in DCM. In this study, the cardiomyocyte specific CREG knock-out and CREG transgenic mice have been successfully established and will be used to prepare animal models and cell models of DCM to determine the role of CREG both in vivo and in vitro. Then by taking advantage of protein microarray assay, the molecular mechanism of CREG in regulating DCM will be elucidated, mainly focusing on the lysosome-autophagy pathway. Results from this study will provide strong theoretical support and novel therapeutic target for prevention and treatment of DCM.