糖尿病性心肌病发病机制尚不完全明确，目前缺少特效治疗手段。我们的前期研究结果显示HIPK2在链脲佐菌素（STZ）诱导的I型糖尿病心肌病模型的心肌组织中显著上调，并初步发现SUMO-1是HIPK2的一个下游分子，HIPK2可以负向调控SUMO-1。在本项目中，我们拟基于新生大鼠心肌细胞、心脏成纤维细胞和STZ诱导的小鼠糖尿病心肌病模型，进行HIPK2的功能获得性和缺失性实验，明确HIPK2对糖尿病诱导的心肌结构和功能损伤的调控作用。机制方面，我们计划通过体内外功能挽救实验，明确HIPK2介导心肌细胞凋亡和心脏成纤维细胞活化过程中的下游基因及其作用方式。本项目将阐明HIPK2在糖尿病心肌病相关心肌细胞凋亡和心肌纤维化中的作用及分子机制，抑制HIPK2有望成为新的糖尿病心肌病防治靶点。

Molecular mechanisms involved in pathogenesis of diabetic cardiomyopathy remain elusive, and novel therapeutic approaches are still required for effective treatment of diabetic cardiomyopathy. Our preliminary results demonstrated that HIPK2 was upregulated in streptozotocin (STZ)-induced diabetic cardiomyopathy mice model; and SIMO-1 was a potential downstream molecule of HIPK2. In this project, we plan to conduct gain-of-function and lost-of-function assays of HIPK2 in hyperglycemia-induced cardiomyocyte apoptosis and cardiac fibroblast activation model and in STZ-induced diabetic cardiomyopathy mice model to clarify the role of HIPK2 in diabetic cardiomyopathy. Furthermore, we will explore the underlying mechanism of HIPK2-mediated apoptosis and fibrosis by means of in vitro and in vivo rescue experiments. HIPK2 inhibition may be a potential solution for prevention and treatment of cardiac structural and functional morbidity in diabetic cardiomyopathy.