慢性缺血性皮肤的细胞外基质代谢异常:腿部皮肤溃疡的一个发生机制

作     者：Dalton S. J. Mitchell D. C. Whiting C. V. Tarlton J.F. 李翠华(译) 

作者机构：Department of Vascular Surgery Southmead Hospital Bristol United Kingdom 不详 

出 版 物：《世界核心医学期刊文摘（皮肤病学分册）》 (Digest of the World Core Medical JOurnals:Dermatology)

年 卷 期：2006年第2卷第3期

页      面：19-20页

学科分类：1002[医学-临床医学] 100210[医学-外科学(含：普外、骨外、泌尿外、胸心外、神外、整形、烧伤、野战外)] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

主　　题：细胞外基质(ECM) 缺血性肢体 皮肤溃疡 代谢异常 慢性 ELISA测定 Western印迹法 全膝关节置换术 基质金属蛋白酶 MMP-9 

摘      要：Extracellularmatrix (ECM) metabolism and homeostasis is sensitive to changes in oxygen tension manifest in ischemia. We hypothesize that in chronically ischemic limbs, abnormalities in uninjured skin, secondary to hypoxia, predispose to dermal breakdown. Paired biopsies of uninjured distal ischemic and proximal non-ischemic skin were harvested at below knee amputation from 14 patients with peripheral vascular disease following quantification of ischemia. Age- and site-matched controls were taken at total knee replacement (TKR) and varicose vein (VV) operations. Matrix metalloproteinase (MMP)- 2 and - 9 expression was determined using gelatin zymography, MMP- 1 by western blotting and ELISA and tissue inhibitor of MMP (TIMP) by reverse zymography. Collagen content was measured by determining hydroxyproline levels, and collagen type I synthesis by ELISA. Collagen type I synthesis was upregulated in ischemic tissue compared with non-ischemic matched pairs (p 0.001) and both TKR and VV controls, however, there was no increase in collagen deposition. Levels of MMP- 2 (p0.0005) and TIMP- 2 (p0.01), were elevated in ischemic samples. MMP- 9 was unaltered, signifying no inflammator changes. Tissue ischemia was linked to elevated ECM turnover, associated with matrix failure when compounded with problems of matrix stabilization, likely in ischemia. This represents a potential mechanism for ulcer formation.