促进心肌血管新生是改善2型糖尿病并发心肌梗死的有效途径，探索血管内皮祖细胞(EPC)新的调控机制是改善心肌血管新生的重要策略。NLRP3炎性小体活化Caspase-1，导致GSDMD依赖的细胞焦亡，同时促进IL-1β与IL-18成熟和分泌；我们多年的研究聚焦NLRP3炎性小体在心血管疾病中的病理作用。本项目利用NLRP3或ASC基因敲除小鼠建立糖尿病合并心肌梗死模型，并且提取2型糖尿病并发心梗患者外周血EPC，研究NLRP3炎性小体通过GSDMD依赖的细胞焦亡，调控EPC功能的机制。同时分析NLRP3或ASC基因敲除的EPC促进心肌血管新生，改善2型糖尿病小鼠合并心梗的心功能和病理损伤。最后，基于NLRP3炎性小体/GSDMD信号通路，深入分析大黄的天然提取物大精酸通过EPC对2型糖尿病合并心梗的改善作用。本项目揭示了EPC新的调控机理，为防治2型糖尿病心血管并发症提供新的靶点和治疗药物。

Promoting myocardial angiogenesis is a valid approach to 2 type diabetes-induced myocardial infarction, and the study of the new mechanisms of EPC regulation is an important strategy in promoting myocardial angiogenesis. NLRP3 inflammasome activated caspase-1 to result in GSDMD-dependent pyroptosis and the maturation and secretion of IL-1β and IL-18. Our studies focus on the roles and mechanisms of NLRP3 inflammasome in the pathogenesis of cardiovascular diseases. Wild-type and NLRP3 or ASC gene knockout mice are used to establish the model of diabetes-induced myocardial infarction, and EPC from 2 type diabetic patients complicated with myocardial infarction are used in current study. It is investigated that NLRP3 inflammasome regulates EPC function through GSDMD-dependent pyroptosis, and NLRP3 or ASC gene knockout EPC transplantation promotes cardiac function and improves pathological injury during myocardial infarction in diabetic mice. Lastly, based on the NLRP3 inflammasome/GSDMD signal pathway, it is tested that argirein, natural product extracted from rheum officinale, alleviates myocardial infarction through improving EPC function in 2 type diabetes. Our studies reveal new mechanisms of EPC regultion, which provides new target of drug action and new drug to prevent and treat cardiovascular complication induced by 2 type diabetes.