下肢慢性静脉溃疡与基质金属蛋白酶相关性的研究进展

下肢慢性静脉溃疡是慢性静脉性疾病的常见和难治并发症,典型表现为下肢慢性溃疡和疼痛.基质金属蛋白酶是一类高度保守的锌依赖的内切蛋白酶,根据底物及结构差异,基质金属蛋白酶分为6类,其中胶原酶、明胶酶、间质溶解素三类在下肢慢性静脉溃疡发生、发展中起重要作用,基质金属蛋白酶1、2、3、8以及基质金属蛋白酶2与基质金属蛋白酶组织抑制因子2比例上调与溃疡愈合延迟有关,基质金属蛋白酶7、10、13和基质金属蛋白酶组织抑制因子1、2上调有利于溃疡愈合,而基质金属蛋白酶9、12在静脉溃疡中的作用尚需进一步研究.结合某些基质金属蛋白酶的功能特征,通过干预其合成及功能,可为下肢慢性静脉溃疡的治疗提供新的靶位.

Correlations between chronic venous leg ulcer and matrix metalloproteinases

Chronic venous leg ulcer (CVLU) is a common and refractory complication of chronic venous diseases,and is clinically characterized by chronic leg ulcers and pain.Matrix metalloproteinases (MMPs) are a kind of highly conservative and zinc-dependent endopeptidases,and can be divided into 6 types according to their substrates and structures.Among the 6 types,collagenases,gelatinases and stromelysins play a key role in the occurrence and development of CVLU.Moreover,the up-regulation of MMP-1,-2,-3,-8 and ratio of MMP-2 to tissue inhibitor of metalloproteinase-2(TIMP-2) is associated with delayed ulcer healing,whereas the up-regulation of MMP-7,-10,-13 and TIMP-1,-2 facilitates ulcer healing.However,roles of MMP-9 and-12 in venous ulcers are still unclear and need further study.According to functional characteristics of some MMPs,intervention of their composition and functions may provide new therapeutic targets for the treatment of CVLU.