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目的了解基质金属蛋白酶－２（ＭＭＰ－２）及其组织型抑制剂（ＴＩＭＰ－２）在纤维化过程中的变化，分析它们在始动阶段的作用。方法用免疫组化和酶图法，在异种血清诱导的大鼠肝纤维化模型不同阶段，作肝细胞内ＭＭＰ－２、ＴＩＭＰ－２、酶降解底物Ⅳ型胶原（ＣｏｌⅣ）以及结蛋白（Ｄｍ）定位和半定量研究。结果实验鼠于４周末形成细胞间隔，８周末发展为肝纤维化，含细胞－纤维间隔或纤维间隔，１２、１６周仍为纤维间隔。酶图法表明４周末ＭＭＰ－２活性升高２．５倍左右，８周末仍高于对照鼠。免疫组化显示４周末ＭＭＰ－２阳性细胞数最多，连续切片观察ＭＭＰ－２与Ｄｍ阳性细胞（活化的肝星状细胞）几乎重叠。８周末阳性细胞数有所减少，１２周末明显减少。半定量变化趋势与酶图法一致。ＴＩＭＰ－２于８周末表达开始升高，１２周末达最高。２周末ＣｏｌⅣ表达开始上升，４周末达高峰，以后缓慢下降。结论肝纤维化早期ＭＭＰ－２活性增高，继而ＴＩＭＰ－２分泌过多，ＭＭＰ－２活性受抑，ＥＣＭ降解受阻，纤维化进一步发展。
Objective To investigate the changes of matrix metalloproteinase-2 (MMP-2) and its tissue inhibitor of metalloproteinase-2 (TIMP-2) in the process of fibrosis and to analyze the role of MMP-2 in the process of initiation. Methods Immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) were used to detect the expressions of MMP-2, TIMP-2, Col Ⅳ and Hs-CRP in rat hepatic fibrosis induced by xenograft Dm) localization and semi-quantitative studies. Results At the end of 4 weeks, the experimental mice formed intercellular spaces, developed hepatic fibrosis at the end of the 8th week, with cell-fiber interphase or inter-fiber interocular space, and remained fibrillar space at the 12th and 16th week. Enzyme-linked immunosorbent assay showed that the activity of MMP-2 increased about 2.5-fold at the end of the 4th week and remained higher than that of the control group at the end of the 8th week. Immunohistochemistry showed that the number of MMP-2 positive cells at the end of 4 weeks was the highest, and the serial overlap showed that MMP-2 and Dm positive cells (activated hepatic stellate cells) almost overlapped. The number of positive cells decreased on the 8th week and decreased significantly on the 12th week. Semi-quantitative changes in the same trend with the enzyme map. The expression of TIMP-2 began to increase at the end of 8th week, reaching the highest at 12th week. The expression of ColⅣ began to rise at the end of 2 weeks and peaked at 4 weeks, then decreased slowly. Conclusion The activity of MMP-2 is increased in the early stage of hepatic fibrosis, then the secretion of TIMP-2 is excessive, the activity of MMP-2 is inhibited, the degradation of ECM is hindered and fibrosis further develops.