下肢慢性静脉溃疡与基质金属蛋白酶相关性的研究进展

Correlations between chronic venous leg ulcer and matrix metalloproteinases

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。

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.