糖尿病皮肤“隐性损害”的机制研究  

Research on olfactory mechanism of the cutaneous “underlying disorder” in diabetic rats

作　　者：陆树良[1] 青春[1] 谢挺[1] 葛奎[1] 牛轶雯[1] 董炜[1] 戎柳[1] 林炜栋[1] 史济湘[1] 

机构地区：[1]上海第二医科大学附属瑞金医院,上海市烧伤研究所,200025

出　　处：《中华创伤杂志》2004年第8期468-473,共6页Chinese Journal of Trauma

基　　金：国家重点基础研究发展规划项目资助 (G19990 5 42 0 5)

摘　　要：目的　明确糖尿病皮肤的伤前病理改变是创面难愈的潜在机制。　方法　体重2 0 0～ 2 2 0 g的SPF级SD大鼠 14只 ,分为糖尿病组 (8只 )和正常对照组 (6只 ) ,以链脲佐菌素(STZ)诱导糖尿病大鼠模型 ,成模后 8周与正常对照组同时采集背部皮肤 ,观察皮肤的组织学特征 ,检测表皮细胞周期 ,测定皮肤组织糖含量、糖基化终末产物 (AGEs)蓄积程度、羟脯氨酸含量、Ⅰ型和Ⅲ型胶原、碱性成纤维细胞生长因子 (bFGF)表达量及其被糖基化程度、髓过氧化物酶 (MPO)含量以及基质金属蛋白酶 - 2 (MMP - 2 )活性和基质金属蛋白酶抑制因子 - 2 (TIMP - 2 )水平。　结果　糖尿病皮肤表皮细胞层次欠清晰 ,部分表皮细胞缺乏复层排列 ,棘细胞数量明显减少 ,表皮层厚度明显变薄 ;糖尿病大鼠皮肤真皮层明显变薄 ,胶原纤细、排列紊乱 ,Ⅲ型胶原分泌增加 ,Ⅰ、Ⅲ胶原交织排列 ,部分胶原可见变性、肿胀 ,胶原变性区域可见慢性炎性细胞局灶性浸润 ;糖尿病大鼠皮肤组织糖含量明显高于正常对照组 ,AGEs明显蓄积 ;糖尿病大鼠皮肤S期以及G2 /M期的表皮细胞百分比明显低于正常对照组 ;糖尿病皮肤局部bFGF释放和表达虽不少于正常皮肤 ,但存在明显的bFGF糖基化 ;此外 ,糖尿病大鼠皮肤组织MPO含量明显增多、MMP - 2活性明显增加 ,活化的MMP -Objective To make sure that the pre-injury pathophysiological changes of diabetic skin is the potential mechanism for olfactory wound healing. Methods A total of 14 SD rats weighing 200-220g were divided into control and STZ-induced diabetes groups. At the 8th week post STZ induction, the shaved skin specimens from the back of rats in both groups were collected to observe the histological characteristics of the skin and determine the local contents of glucose, advanced glycation end products (AGEs), myeloperoxidase (MPO) and hydroxyproline, the expressions of bFGF and its type Ⅰ and Ⅲ collagens, the sensitivity of MMP-2 (全称) and the levels of tissue inhibitor of metalloproteinase-2 (TIMP-2) and the cell cycles of keratinocytes. Results In diabetic skin, the thickness of epidermis layer was reduced obviously with obscure multilayer epithelium features and less amount of prickle cells in epidermis. The dermis layer became thinner with tenuous collagen distributing disorderly as well as increased secretion of type Ⅲ collagens and cross distribution of type Ⅰ and Ⅲ collagens, part of which went atrophy and swollen and degenerated collagen fibers with a focal chronic inflammatory cell infiltration. In diabetic group, the percentage of keratinocytes at stages S and G 2/M were obviously lower than that in the control group. Contents of glucose, AGEs, MPO and hydroxyproline, the level of aMMP-2 and the ratio of aMMP-2 / TIMP-2 in diabetic skin were higher than those in the controls. The positive expression of bFGF was not decreased, but expression of bFGF in diabetic skin was obviously glycated. Conclusions The cutaneous histological and pathophysiological alterations in diabetes mellitus exist before skin wound, which is a kind of “underlying disorder” that may give rise to ulceration in diabetic skin and be one of the most important mechanisms in the pathogenesis of impaired wound healing.

关 键 词：糖尿病 皮肤 表皮细胞 组织学 病理生理学 

分 类 号：R587.2[医药卫生—内分泌]