MMP-2、TIMP-2、CD147在中医药防治肝纤维化中的作用

Effects of MMP-2,TIMP-2 and CD147 in the TCM Prevention and Treatment of Liver Fibrosis

基质金属蛋白酶-2(matrix metalloproteinase-2,MMP-2)是降解Ⅳ型胶原的主要酶,基质金属蛋白酶组织抑制剂-2(tissue inhibitor of metalloproteinase-2,TIMP-2)是其天然抑制剂,二者也是维持细胞外基质(extra cellular matrix,ECM)正常代谢的关键。CD147又被称为细胞外基质金属蛋白酶诱导因子,是MMP-2活化过程中的重要因子。越来越多的研究发现,中医药可通过影响MMPs/TIMPs的表达来防治肝纤维化。中医药学家通过大量的临床和实验研究来防治肝纤维化,并取得了很大的进展,但仍有很多现实问题。临床实际中各中医学家对肝纤维化阶段的辨证着眼点不同,易忽视与其他脏腑之间关系,正确把握"祛邪与扶正"的关系值得进一步探讨。基础研究相对滞后,体外实验研究的局限性,缺乏与人体肝纤维化相近的模型,天然中药成分复杂,中药复方作用机理更加难以阐明,阻碍了中医药防治肝纤维化的应用。中药来源、处理等过程不同,起作用的生物活性物质所用含量有差别,难以对研究结果进行比较。但中药种类丰富,具有多成分、多层次、多途径、多靶点的综合药理作用,可以对肝纤维化复杂的病理过程进行应对,在此方面充分显示了优势,也显示出中医药在防治肝纤维化方面的前景。肝纤维化产生机制复杂,寻求有效的防治肝纤维化之路、逆转早期肝纤维化及延缓肝硬化甚至肝癌的进程有很重要的现实意义,我们还需要不懈的努力和继续进行探索。

MMP-2 is a main enzyme for degrating IV type collage. TIMP-2 is a natural inhibitor. Both are key to maintain normal metabolism of ECM. CD147 refers to extracellular matrix metallopmteinase and is an important factor in the activated process of MMP-2. It is discovered by more and more research that Chinese medicine can prevent and treat liver fibrosis by affecting the expression of MMPs/TIMPs. Chinese medicine practitioners prevent and treat liver fibrosis through a great number of clinical practice and experimental research, and they have achieve great progress, but there are still some practical problems. In clinical prac- tice, practitioners focus differently and tend to ignore the relation with other viscera. The correct managing the relationship between ＂eliminating the pathogen and reinforcing the healthy qi＂ needs further exploration. Relative lagging-behind basic research,limited in vitro experimental research, lack of models similar to liver fibrosis of the man, complicated natural Chinese medicine components and difficulties of expounding of the action mechanism of the compound formula impede the application of Chinese medicine to the prevention and treatment of liver fibrosis. Different sources and treatment process of the Chinese medicine, difference in the content of the acting bioactivator make it difficult to compare the research results. But there are a wide variety of Chinese medicine categories with the comprehensive pharmacological action of multiple constituents, levels, routes and targets, which enable the dealing with the complex pathological process of liver fibrosis. In this aspect, it shows the advantage and the prospect of TCM in preventing and treating liver fibrosis. The generation mechanism of liver fibrosis is complex. Searching for effective prevention and treatment of liver fibrosis ,reversing the liver fibrosis at early stage and delay the liver cirrhosis even the process of liver cancer have great practical significance. We need to make unremitting efforts and continue the exploration.