肝再生过程中肝星状细胞及基质金属蛋白酶的动态变化

Dynamic Change of Rat Hepatic Stellate Cells and the Expression of Matrix Metalloproteinases During its Regenerative Process

目的研究大鼠肝大部切除(PH)后再生过程中肝星状细胞(HSCs)的动态变化及肝MMP-2、MMP-9的活性变化,探讨肝星状细胞在肝再生中的作用。方法按Higgins等方法制备肝大部切除动物模型,于术后恢复不同时程取材,免疫组织化学法检测肝HSCs的动态变化,明胶酶谱电泳法检测肝中MMP-2、MMP-9的变化。结果(1)正常肝小叶内HSCs呈网架状分布,PH后Desmin阳性HSCs的数量递减;胶质纤维酸性蛋白(GFAP)阳性HSCs的数量也呈递减趋势。(2)PH后再生过程中,肝脏MMP-2、MMP-9的表达逐渐增多。结论肝再生过程中HSCs的增殖反应较慢且维持的时间短,这不同于肝纤维化等肝病过程中HSCs维持较长时间的激活状态。肝再生过程中基质金属蛋白酶-2,-9的表达发生显著改变,提示基质金属蛋白酶-2,-9参与了肝再生过程。

Objective To investigate the dynamic change of hepatic stellate cells （HSCs） and the activities of MMP-2 and MMP-9 in rat liver during its regenerative process after 2/3 hepatectomy （partial hepatectomy,PH）. Methods Rats were subjected to subtotal hepatectomy according to the method of Higgins and Anderson. After PH, regenerating livers were prepared at different time points. Expression of desmin and GFAP in HSCs were observed by immunohistochemistry and the activities of matrix metalloproteinase-2（MMP-2） and matrix metalloproteinase-9（MMP-9） were detected by SDS-G-PAGE. Results （1） HSCs were extensively distributed in liver lobules and constituted the supporting network. Both the number of desmin and GFAP positive HSCs declined. （2） During liver regeneration, the expression of MMP-2 and MMP-9 increased gradually. Conclusion The proliferative response of HSCs in regenerating liver after PH was slow and its duration was short, which were different from that in the liver fibrosis or injure. Moreover, the expression of MMP-2 and MMP-9 changed remarkably during the liver regeneration, indicating the MMP-2 and MMP-9 may participate this process.