Ⅱ型糖尿病（DM）创面难愈是临床和基础研究热点，而血管内皮细胞（EC）功能异常是其主要机制之一。我团队前期发现，连接黏附分子A（JAM-A）在DM创面血管EC中上调且正性调控IL-16。结合国内外研究，我们假设：DM创面的血管EC过表达JAM-A，直接结合并上调IL-16，影响血管EC增殖迁移，恶化炎症环境，延迟创面愈合。本研究拟行：①明确DM血管EC的JAM-A和IL-16直接结合并表达上调；②验证过表达/沉默JAM-A，IL-16相应改变，影响血管EC增殖迁移分泌；③证实拮抗JAM-A或IL-16能恢复EC功能，减轻炎症，促进愈合；④基因芯片筛选影响创面愈合的差异基因，构建共表达网络探索潜在机制。本研究从临床标本、原代细胞、基因、蛋白、体外、体内层层深入，全面阐释JAM-A在DM中对血管EC增殖迁移分泌功能的影响及机制，为新药研发提供全新可靠的理论依据，增添创面修复新的药物靶点。

Nonhealing wounds of Type Ⅱ diabetes mellitus (DM) have always been a clinical difficulty and research focus. Recent studies have shown that vascular endothelial cell (EC) dysfunction is one of the important mechanisms of that. Our team previously found that junctional adhesion molecule A (JAM-A) was up-regulated in vascular EC from DM wounds, and might positively regulate interleukin-16 (IL-16). Therefore, combined with domestic and foreign researches, we come up with the hypothesis: in type Ⅱ DM, damaged vascular ECs induce overexpression of JAM-A, followed by direct interact with IL-16; up-regulated IL-16 can affect the proliferation and migration of vascular ECs, deteriorating the inflammatory environment and delaying the wound healing. In this proposed study, we will (1) collect wound samples from DM patients to determine whether JAM-A and IL-16 are significantly up-regulated and whether they can combine with each other; (2) increasing or silencing the expression of JAM-A to observe changes of IL-16 and alterations in the proliferation and migration of vascular ECs;(3) Specifically antagonize JAM-A or IL-16 in db/db mouse model to observe whether wound healing is promoted and inflammation is inhibited; (4) comprehensively screen for differentially expressed genes in vascular ECs from DM patients by Gene chips, and construct co-expression networks to explore the underlying mechanisms. This study starts from clinical samples to primary cells, genes, proteins, in vitro layers, in vivo layers steps by steps and attempts to clarify the effects and mechanisms of JAM-A on the functions of vascular ECs in DM wounds, and to provide a new biological target, which is of great theoretical importance and application value.