糖尿病合并心肌梗死的高致死率是临床亟待解决的科学问题。探寻糖尿病合并心肌梗死的有效防治手段十分必要。本项目初步研究显示糖尿病小鼠心肌梗死后心脏中NAD+水平显著降低，补充NAD+能够改善糖尿病小鼠心肌梗死后的心脏损伤，同时抑制lncRNA-Lhx1os的表达，促进巨噬细胞分泌VEGF，促进心脏血管新生。此外，前期研究发现GDF11具有上调NAD+的作用。因此，本项目旨在（1）确定补充NAD+可以成为糖尿病合并心肌梗死损伤的治疗方法；（2）阐明NAD+靶向lncRNA-Lhx1os/LHX1/Wnt通路介导巨噬细胞分泌VEGF，改善糖尿病合并心肌梗死损伤；（3）揭示GDF11上调NAD+的机制及对糖尿病合并心肌梗死损伤的潜在治疗作用。（4）探讨外周血中NAD+作为糖尿病合并心肌梗死预警因子的可能性。从疾病预警、药物治疗和药物靶点筛选三个方面为临床糖尿病合并心肌梗死的防治提供思路。

The high mortality of diabetic patients with myocardial infarction is a scientific issue to be solved urgently in clinic. It is necessary to explore effective prevention and treatment methods for diabetes complicated with myocardial infarction. Preliminary research in this project showed that NAD+ levels were reduced in the heart of diabetic mice after myocardial infarction. NAD+ could improve the cardiac function of diabetic mice after myocardial infarction, simultaneously inhibit the expression of lncRNA-Lhx1os, promote the secretion of VEGF in macrophages and promote cardiac angiogenesis. In addition, we have found that GDF11 was an endogenous molecule that up-regulated NAD+. Therefore, this project aims to (1) determine that NAD+ supplementation can be a treatment method for diabetic patients with myocardial infarction; (2) clarify that NAD+ targets lncRNA-Lhx1os/LHX1/Wnt pathway to mediate macrophages VEGF secretion and improve diabetic patients with myocardial infarction; (3) reveal the mechanism of GDF11 in up-regulating NAD+ and the potential therapeutic effect of GDF11 on diabetes with myocardial infarction; (4) evaluate the possibility of NAD+ in peripheral blood as a predictor for diabetes complicated with myocardial infarction. From prediction, treatment and targets screening, our project provides ideas for the prevention and treatment of diabetic patients with myocardial infarction.