我们前期研究发现HDL调节内皮细胞中ANXA1参与HDL的抗炎保护功能。而在糖尿病状态下，申请人实验室发现糖尿病患者HDL的糖基化水平明显升高，并且糖尿病患者HDL促进内皮细胞增殖、迁移以及细胞外基质黏附的能力降低。我们推测ANXA1能够通过发挥抗炎作用或调节脂质连接和代谢的方式调节血管内皮细胞的损伤修复和血管新生，同时在糖尿病的状态下，ANXA1的这种能力会受到影响。我们首先将采用脂质组学和代谢组学的方式发现ANXA1影响到的差异性脂质或代谢产物，采用蛋白组学技术发现在糖尿病状态下ANXA1可能发生的变化，接着我们通过细胞实验证明ANXA1的表达与血管内皮细胞以及炎症反应的关系，然后经过全身与内皮特异敲除ANXA1动物模型验证其对血管内皮损伤修复、表皮损伤修复和缺血性血管新生的影响并进一步研究其作用机制和信号通路。整项研究将为糖尿病血管病变的机制和治疗提供新的思路。

In our previously research, we found that HDL plays important role in anti-inflammation and vascular protection through regulating ANXA1.In diabetic patients, HDL had a obviously increasing glycation level.Besides, the ability of promoting the proliferation and migration of vascular endothelial cells fall down.We suppose ANXA1 can promote vascular injury repair and angiogenesis through anti-inflammation or regulating the metabolism of lipids.Meanwhile, under the condition of diabetes, this ability will fall.We will first use lipidomics and metabonomics methods to find the different lipids or metabolins and proteomics to find the possible changes of ANXA1 under diabetic condition.Then we will clarify the relationship among ANXA1 expression, the function of vascular endothelial cells and inflammatory reaction by cell experiments.Next, ANXA1-/- and ANXA1 endothelial specific knockout animal will be used to confirm that ANXA1 will promote vascular injury repair and ischemia angiogenesis and study the molecular mechanism and pathways.The whole research will provide new understandings in the mechanism and treatments of diabetic angiopathy.