引起糖尿病血管并发症最主要的病因是血管重构，而慢性炎症和氧化应激是引起血管重构的主要因素。新近研究表明FoxO1在调节慢性炎症和氧化应激方面具有重要作用。我们预实验发现糖尿病小鼠颈动脉中，FoxO1表达水平增高并穿梭至细胞核，伴随NLRP3炎症小体表达增加和氧化应激加重，继而引起细胞凋亡并导致血管中膜平滑肌细胞由收缩表型转换为增殖表型，加重糖尿病血管重构。因此推测，FoxO1/NLRP3信号通路异常是糖尿病血管重构的关键机制。本项目拟结合基因敲除或药物抑制，在糖尿病小鼠颈动脉与人主动脉平滑肌细胞上探索FoxO1/NLRP3信号通路调控慢性炎症和氧化应激的分子机制及对血管重构的影响，为研发糖尿病血管并发症的防治措施提供新的思路。

Vascular remodeling is the main cause of diabetic vascular complications, while chronic inflammation and oxidative stress are the potential factor of vascular remodeling. Recent studies have shown that FoxO1 plays an important role in regulating chronic inflammation and oxidative stress. Our preliminary experiments found that in diabetic mice carotid artery, FoxO1 expression is enhanced and then transferred into the nucleus, accompanied by increased expression of NLRP3 inflamsome and oxidative stress, subsequently leading to apoptosis and phenotype switching of vascular smooth muscle cells from contraction subtype to proliferation subtype, which finally aggravates diabetic vascular remodeling. Thus, we speculate that FoxO1/NLRP3 signaling pathway dysfunction is critical in diabetic vascular remodeling. The this study is to explore the molecular mechanism of FoxO1/NLRP3 signaling pathway regulation on chronic inflammation and oxidative stress in diabetic mice carotid artery and human aortic smooth muscle cells by gene knockout or drug inhibition, and to provide a new idea for the prevention and treatment of diabetic vascular complications.