糖尿病心肌病引起心脏功能障碍，导致临床心力衰竭，心源性休克，甚至猝死。然而，临床上缺乏有效的治疗方法。近年研究显示，Notch3能明显改善病理性心脏心功能，但Notch3是否能够减轻糖尿病心肌病心肌损伤，目前还未见相关报道。我们前期研究发现，敲除Mst1能够促进心肌细胞自噬，抑制凋亡，改善糖尿病小鼠心功能；同时，Notch3能够靶向抑制Mst1表达及其磷酸化。结合预实验结果分析，我们提出Notch3可能通过抑制心肌细胞Mst1的表达及其磷酸化，进而促进心肌细胞自噬，抑制凋亡，从而抑制糖尿病心肌病的发生发展。本项目旨在探讨Notch3/Mst1信号通路在糖尿病心肌病中的作用及其分子机制，有望为糖尿病心肌病的防治提供新的思路和实验依据。

Diabetic cardiomyopathy causes cardiac dysfunction, leading to clinical heart failure, cardiogenic shock, and even sudden death. However, there was still lack of efficient therapeutic methods in clinic. Recent studies revealed that Notch3 could significantly improve pathological heart function. However, whether Notch3 could reduce myocardial injury in diabetic cardiomyopathy has not been reported yet. Our previous study found that Mst1 knockout could promote autophagy and inhibit apoptosis in cardiomyocytes, and improve cardiac function in diabetic mice. Notch3 could also inhibit Mst1 expression and its phosphorylation. Combined with the analysis of preliminary experimental results, we propose that Notch3 may promote autophagy and inhibit apoptosis by inhibiting the expression and phosphorylation of Mst1 in cardiomyocytes, thereby inhibiting the occurrence and development of diabetic cardiomyopathy. The purpose of this project is to explore the role of Notch3/Mst1 signaling pathway in diabetic cardiomyopathy and its molecular mechanism, which is expected to provide new ideas and experimental basis for the prevention and treatment of diabetic cardiomyopathy.