大鼠肝纤维化模型中基质金属蛋白酶-2及其抑制物的表达  

Expression of Matrix Metalloproteinase2 and It's Tissue Inhibitor in Rat Liver Fibrosis Model

作　　者：吴运瑾[1] 翟为溶[1] 庄丽[1] 张月娥[1] 朱虹光[1] 

机构地区：[1]上海医科大学基础医学院病理学教研室

出　　处：《上海医科大学学报》1999年第4期261-264,共4页Journal of Fudan University(Medical Science)

基　　金：国家自然科学基金;上海市教委重点学科(病理学)资助

摘　　要：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。Purpose To observe the changes of matrix metalloproteinase2(MMP2) and its tissue inhibitor in rat liver fibrosis,and to clarify how they participate in liver fibrogenesis,particularly in the early stage of the di sease . Methods By immunohistochemistry and zymography,the expression of MMP2,TIMP2,desmin(Dm) and collagen type Ⅳ(Col Ⅳ) were detected in rat fibrotic liver induced by injection of porcine serum. Results Cellular septa appeared in the liver at the end of the 4 th week after injection.At the end of the 8 th or 12 th week,all the experimental rats showed mixed septa of cellular and fibrillar or fibrillar septa.Zymogram showed that the activity of MMP2 in the experimental rats was markedly elevated at the end of the 4 th or 8 th week,especially at the 4 th week,and was 2.5 times to that of the control groups. By immunohistochemistry,numerous MMP2 positive cells could be found in cellular septa,and the perisinusoid of intralobules at the 4 th week.The majority of MMP2 positive cells were Dm positive.At the 8 th week,the number of MMP2 positive cells was decreased.After the discontinuation of injection,MMP2 positive cells were further decreased.These changes were coincident with the above zymographic results.Increased expression of TIMP2 was found at the end of the 8 th week,being highest at the 12 th week.The expression of ColⅣ was increased at the end of the second week,being highest at the 4 th week,then dec reased slowly. Conclusions The activity of MMP2 was increased in the early stage of liver fibrogenesis,then was inhibited by the increased expression of TIMP2,the degradation of ECM will be disrupted,and the deposition of ECM will be more and more.

关 键 词：肝纤维化 基质金属蛋白酶 TIMP-2 MMP-2 

分 类 号：R575.202[医药卫生—消化系统]