糖基化基质对人皮肤成纤维细胞增殖凋亡平衡的研究  

Effects of extracellular matrix glycation on the balance of proliferation and apoptosis in human dermal fibroblasts

作　　者：牛轶雯[1] 谢挺 缪明远[1] 葛奎[1] 陆树良[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院烧伤整形科,上海市烧伤研究所,200025 [2]湖北省武汉市第三医院烧伤科

出　　处：《中国糖尿病杂志》2009年第11期853-856,共4页Chinese Journal of Diabetes

基　　金：国家自然科学基金项目(30471784,30570705,30600645)

摘　　要：目的探讨糖尿病皮肤细胞外基质(ECM)糖基化改变与细胞增殖凋亡平衡的相关性。方法 DM或非DM患者的皮肤组织和溃疡创面标本组织学观察,同时免疫组化法检测皮肤组织增殖细胞核抗原(PCNA)、凋亡细胞、糖基化终末产物(AGE)和糖基化终末产物受体(RAGE)表达;体外建立糖基化基质,RAGE抗体干预后,检测细胞存活率、细胞周期和凋亡。结果与对照组相比,DM皮肤胶原萎缩,凋亡细胞比例增高;创面肉芽形成不良,细胞增殖能力减弱,凋亡细胞增加,AGE和RAGE表达增多;体外糖基化基质上接种成纤维细胞存活率明显减少,细胞周期运行障碍,凋亡增加,阻断AGE-RAGE间相互作用可基本缓解糖基化基质对细胞增殖凋亡过程的影响。结论 DM皮肤组织中糖基化ECM蓄积是细胞功能改变的重要环境介质,经RAGE介导影响细胞增殖凋亡平衡,致糖尿病皮肤创伤起点异常,创面难愈。Objective To investigate the effects of glycosylation-induced dermal microenvironment alteration on the balance of cellular proliferation and apoptosis in diabetes. Methods Histology and immunohistochemical staining were performed on type 2 diabetic and non-diabetic skin and wound tissue specimens to determine distributions of proliferating cell nuclear antigen（PCNA）, apoptotic ceils, AGEs, and RAGE. In vitro, matrix secreted by human FB was glycosylated by 0.5M D-ribose. RAGE blocking antibody was applied to clarify the possible mechanisms. Results Diabetic skin had degenerative, loosely arranged collagen and increased apoptotic cells as compared to normal skin. In diabetic wound healing, a decreased proliferative capacity and increased apoptosis of FB may contribute to the impaired formation of granulations. Expression of AGE and RAGE in diabetic skin tissue was increased. In vitro, glycosylated matrix induced cell-cycle arrest and apoptosis of dermal fibroblast, while application of RAGE blocking antibody redressed these changes. Conclusions Glycosylated ECM in diabetic skin is a critical mediator of cellular function changes. Mediation of RAGE affects the balance of cellular proliferation and apoptosis, which damages the healing process of diabetic wounds.

关 键 词：糖尿病 皮肤 创面愈合 细胞凋亡 细胞增殖 糖基化 

分 类 号：R587.1[医药卫生—内分泌]