VEGF/FLT-1/OPN信号通路介导的成纤维细胞增殖和迁移在高压氧促进炎症期糖尿病创面修复的作用机制

糖尿病创面难愈是临床上难以解决的棘手问题。成纤维细胞增殖与功能异常被认为是其病变的重要始动因素，研究表明高压氧（HBO）可刺激成纤维细胞增殖、且骨桥蛋白(OPN) 是促进伤口愈合的重要蛋白，但其机制尚不清楚。我们发现血管内皮生长因子/血管内皮生长因子受体-1（VEGF/FLT-1）信号通路在成纤维细胞迁移中起重要作用，已知该通路可调节OPN的表达，据此我们提出假说：高压氧可能通过成纤维细胞上的VEGF/FLT-1/OPN信号通路促进糖尿病创面早期愈合。本研究将探讨：1) 高压氧能否刺激成纤维细胞VEGF/FLT-1的表达从而影响细胞迁移和增殖功能；2) 探讨VEGF/FLT-1介导的包括OPN在内的下游分子机制；3）在体实验验证VEGF/FLT-1/OPN信号通路是否介导高压氧促进糖尿病创面的早期修复作用。以期为临床寻找糖尿病创面高压氧最佳治疗时机提供理论依据。

Non-healing wound caused by diabetes is a serious problem. The change of the fibroblasts’ function of proliferation and migration is one of the key to this problem. It’s reported that hyperbaric oxygen therapy can stimulate fibroblast’s migration and Osteopontin (OPN) is an important protein to promote wound healing. Our previous study showed that fibroblasts can express VEGF/FLT-1, which plays an important role in the fibroblast’s migration. It’s reported that VEGF/FLT-1 can influence the expression of OPN. Hence, we have a hypothesis that hyperbaric oxygen therapy might stimulate the function of fibroblast through the VEGF/FLT-1-OPN signal pathway to promote the healing of wounds. In this study, we will explore 1) whether HBO stimulate the expression of VEGF/FLT-1 on fibroblasts and affect the fibroblasts’ migration and proliferation. 2) the mechanism of effect of VEGF/FLT-1 on fibroblasts’ function, which might involve OPN. 3) in vivo animal mode to verify whether VEGF/FLT-1/OPN signal pathway is involved in the repair of diabetic wound after HBOT. We hope our findings will help to find a new target of hyperbaric oxygen for diabetic wounds therapy.