基质金属蛋白酶-2在猪胆汁性肝纤维化活性及表达的改变

目的　研究猪胆汁性肝纤维化时基质金属蛋白酶-2（MMP-2）表达及活性改变，分析其在肝纤维化初始阶段的作用。方法　普通猪10头行胆总管结扎术(BDL)前和术后取其肝组织作样本自身对照，用原位杂交法研究MMP-2的mRNA表达改变;用酶图法研究MMP-2活性改变。结果　术后4周原位杂交显示肝星状细胞(HSC)细胞增多、增生、向肝细胞坏死区聚集、胞浆呈强阳性。术前组和术后组平均吸光度分别为0.0246±0.0090和0.0671±0.0091。酶图法表明MMP-2酶原表达是正常的1.68倍（51±6/86±11），活性升高至2.29倍（21±4/48±3），差异均有非常显著性（P＜0.01）。结论　猪胆汁性肝纤维化时HSC增生,其胞浆中MMP-2mRNA表达增多，酶活性增强，MMP-2在肝维化的早期参与ECM的重塑和肝小叶的改建。

The changes of the expression and activity of matrix metalloproteinase-2 in pig liver fibrosis model

Objective To observe the changes of the expression of matrix metalloproteinase 2 (MMP 2) and the activity of MMP 2 in the early stage of liver fibrosis. Methods Ten pig models of common bile duct ligation (BDL) induced hepatic fibrosis were used to assess the expression and activities of MMP 2 during the progression of fibrosis. Expression of MMP 2 was detected by using in situ hybiridization method in liver tissue after hepatic fibrosis developed or the tissue obtained before BDL. In addition free gelatinase activity was analyzed by using zymography. Results Cellular septa appeared in the liver at the end of the 4th week after BDL. Proliferated hepatic stellate cells were accumulated in the necrotic lesion. Disruption of the lobular structure was also found. Bile duct were dilated, filled with pus, and surrounded with fibril. Zymogram showed that the activity of MMP 2 was increased (2.29 times). Proenzyme level was also increased (1.68 times). Statistically significant difference were observed ( P <0.01). Strong positive and proliferated hepatic stellate cells (HSCs) was found in ISH. In normal liver the expression positive for MMP 2 was rather weak. Statistically significant difference was also observed ( P <0.01). Conclusion The activity of MMP 2 was increased in early stage of liver fibrogenesis, suggesting activated MMP 2 may remodel liver parenchyma during the process of liver fibrosis,and HSCs play a central role in the pathogenesis of liver fibrosis. It is possible that up regulation and the increase in gelatinolytic activity of MMP 2 take part in the remodeling process of ECM and hepatic lobule. [