局部转染组织因子促进糖尿病小鼠的伤口愈合  

Improvement of wound healing in diabetic mice by transfecting TF cDNA

作　　者：白玲[1] 姜宗来[1] 陈保生[2] 

机构地区：[1]上海交通大学医学院,上海200240 [2]中国协和医科大学中国医学科学研究院基础医学研究所,北京100005

出　　处：《基础医学与临床》2005年第11期1014-1019,共6页Basic and Clinical Medicine

基　　金：国家自然科学基金(39770168);国家重点基础研究发展规划项目(G-20000569-02)

摘　　要：目的为证实组织因子(TF)在启动新血管生成、促进伤口愈合中有一定的作用。方法我们以伤口愈合迟缓的糖尿病小鼠为研究对象,应用免疫组化,RT-PCR及伤口局部组织因子转染等方法,研究了组织因子在伤口愈合中的作用。结果正常小鼠未创伤皮肤几乎检测不到TF的表达,但创伤时TF的表达明显增高。和正常健康鼠比较,糖尿病鼠伤口处TF、血管内皮细胞生长因子(VEGF)、α平滑肌肌动蛋白(-αSMA)的表达不足,新血管生成迟缓,伤口处血管密度和血流明显减少伴随着伤口愈合的迟缓。以克隆有TF cDNA的真核表达质粒局部转染糖尿病小鼠的皮肤伤口,转染后伤口部位的TF表达明显增高,并明显促进了伤口局部新血管的形成,加速了伤口的愈合。同时促进了VEGF和-αSMA的表达。结论糖尿病鼠伤口愈合迟缓与伤口愈合初期阶段组织因子(TF)的合成不足有关,转染TF基因可以明显改善伤口愈合,其促进伤口愈合与其诱导血管内皮生长因子和α-平滑肌肌动蛋白的合成有关。Objective To prove that TF may p the impaired angiogenesis of non-obese diabetic lay a role in the beginning of the wound healing. Methods We studied mice （NOD） by using immunohistochemical method, RT-PCR and somatic TF gene transfection. Results TF expression was almost undetectable in intact skin, its up-regulation expression occured in hyperplastic epidermis of health mice as soon as the wound excised. Comparing with healthy mice, the expressions of TF. VEGF and α-SMA were significantly reduced during wound healing in diabetic mice and resulted in the wound healing being impaired. To address the importance of TF in skin angiogenesis, we investigated the effect of gene therapy with an eukaryocyte expression plasmid pcDNA3 carrying the TF gene on excised wound in diabetic mice. Conclusion Somatic gene TF transfection improves wound healing by promoting the angiogenesis, increasing capillary density and significantly improves blood flow in the wound. Inadequate TF expression, at least in part, is belioved to be for the delayed wound healing of diabetic mice. TF transfection improves the wound healing in diabetic mice.

关 键 词：糖尿病鼠 伤口愈合 组织因子 血管内皮细胞生长因子 Α-平滑肌肌动蛋白 

分 类 号：R587.1[医药卫生—内分泌]