bFGF对糖尿病溃疡组织中血管内皮细胞氧化应激相关酶调控作用

项目名称： bFGF对糖尿病溃疡组织中血管内皮细胞氧化应激相关酶调控作用

项目编号： No.81201245

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学四处

项目作者： 朱忠欣

作者单位： 温州医科大学

项目金额： 23万元

中文摘要： 糖尿病发病率日益上升，其并发症糖尿病皮肤溃疡的治疗已成为亟待解决的难题之一。目前，临床已成功将外源性生长因子bFGF应用于糖尿病皮肤溃疡的治疗。bFGF促皮肤溃疡修复的主要靶器官之一是与肉芽组织生长密切相关的血管内皮细胞，但其信号传递途径和网络调控作用机制尚不清楚。前期动物模型蛋白质组学研究显示bFGF可显著上调GAPDH的表达，并下调Aldolase、MDH、LDH的表达，此四种蛋白均为糖代谢相关酶，其表达水平和亚细胞定位又与氧化应激及细胞凋亡密切相关，进而提示bFGF可能是通过调控上述蛋白的表达或定位，来减少细胞凋亡、提高增殖能力，产生促修复作用。本课题旨在前期实验基础上进一步研究bFGF对高糖损伤血管内皮细胞中上述四种蛋白的表达、亚细胞定位及蛋白活性的影响，初步探讨bFGF促糖尿病皮肤溃疡修复机制与氧化应激和细胞凋亡的关系，为bFGF临床应用提供理论依据。

中文关键词： 碱性成纤维细胞生长因子；高糖；血管内皮细胞；成纤维细胞；迁移

英文摘要： The incident of diabetes is incresing constantly, and the treatment of diabetic skin ulcer has become a difficult problem in clinic. Nowadays, exogenous growth factor bFGF has successfully been applied to treat diabetic skin ulcer and achieved good curative effect. According to former reports, vascular endothelial cells is one of major bFGF targeted cell type in ulcer skin tissue. However, the mechanism of pathway and network regulation of this process is not yet clear. The former proteomics results showed that bFGF can dramatically up-regulate the expression of GAPDH, and down-regulate the expression of Aldolase, MDH, LDH, what belong to glycometabolism-related enzymes. The expression level and subcellular localization of these proteins are closely related to oxidative stress and apoptosis, which indicate that bFGF may improve proliferation ability, and finally produce reparative effect by regulating the expression or location of these proteins. The purpose of this project is to take further research on the effect of bFGF on the variation of these proteins in vascular endothelial cells injured by high glucose, and then to explore the connection among the mechanism of healing effect of bFGF, oxidative stress, as well as apoptosis. The result of this project will provide a theoretical basis for bFGF application

英文关键词： bFGF；High-glucose；Vascular endothelial cells；Fibroblast cells；migration