糖尿病心肌病是一种由糖尿病引起的心脏结构和功能改变的疾病，最终可导致心衰。目前发病机制尚不明确，缺乏有效治疗。我们以往研究发现双特异性磷酸酶12（DUSP12）通过调节ASK1活性调控脂质合成，但其在糖尿病心肌病中的功能未知。本项目前期研究发现，在糖尿病心肌病小鼠心脏组织及高糖诱导的心肌细胞损伤模型中，DUSP12均显著下调。基于以往研究和前期发现，我们推断DUSP12可能通过ASK1调控糖尿病心肌病的发病。为验证该假说，本项目拟以DUSP12基因敲除和心肌细胞特异性转基因小鼠为研究对象，通过高脂饮食联合链脲佐菌素诱导糖尿病心肌病发生，探讨DUSP12对糖尿病心肌病的影响；在原代心肌细胞中敲低或过表达DUSP12，探究DUSP12对心肌细胞功能的影响；最后在心肌细胞中验证DUSP12对ASK1的调控作用以及评估外源性导入DUSP12对治疗糖尿病心肌病效果，为糖尿病心肌病的治疗提供新的靶点。

Diabetic cardiomyopathy is defined as cardiac structural and functional changes caused by diabetes mellitus, which ultimately lead to heart failure. While the mechanism of its occurrence and development has not been fully elucidated. The previous studies have shown that dual-specificity phosphatase 12 (DUSP12) regulates lipid synthesis by regulating ASK1 activity, however, the functional role of DUSP12 in diabetic cardiomyopathy is unclear. In the preliminary experiment, it is found that the expression of DUSP12 was down-regulated in diabetic cardiomyopathy mice model and high glucose induced cardiomyocyte injury model. Based on the above findings, it hypothesize that DUSP12 may be involved in the pathogenesis of diabetic cardiomyopathy through ASK1. To investigate the effects of DUSP12 in diabetic cardiomyopathy induced by high-fat diet combined with streptozotocin, we intends to use DUSP12 knockout and cardiomyocyte-specific transgenic mice. We then knocked down or overexpressed DUSP12 in primary cardiomyocytes to explore the effects of DUSP12 on the function of cardiomyocytes. Finally, we validated the regulatory effect of DUSP12 on ASK1 in cardiomyocytes, and evaluated the therapeutic effect of exogenous DUSP12 in diabetic cardiomyopathy. This study may provide new clues for the development mechanism and clinical intervention for diabetic cardiomyopathy and the subsequent heart failure.