四氯化碳诱导大鼠肝纤维化过程中ACT βA的表达定位

EXPRESSION AND LOCALIZATION OF ACTIVIN βA IN THE DEVELOPMENT OF RAT HEPATIC FIBROSIS INDUCED BY CARBON TETRACHLORIDE

观察四氯化碳 (CCl4)诱导大鼠肝纤维化形成过程中激活素βA (activinβA ,ACTβA)的表达变化。将 74只雄性SD大鼠随机分成对照组 (n=10 )和模型组 (n=6 4)。 40 % CCl4皮下注射模型组大鼠制备肝纤维化模型 ,注射 CCl41、 2、 3、4、 5、 6及 7周后分批处死 ,每次 6～ 12只。用免疫组织化学法检测各组 ACTβ A、转化生长因子 β1(transforming growthfactorβ1,TGF- β1 )及 α平滑肌激动蛋白 (α- smooth m uscle actin,α- SMA)表达。结果显示正常肝脏表达 ACTβA,CCl4注射 1周后 ,染色范围缩小 ,2～ 3周以后 ,染色明显减弱 ,甚至染色阴性 ,注射 4周后 ,染色又逐渐增强 ,注射 5～ 7周后染色进一步增强。 ACTβA定位于正常肝脏肝细胞胞浆 ,肝纤维化逐渐形成时则分布在中央静脉、汇管区、纤维间隔等纤维化区域周围的肝细胞。随着纤维化程度加重染色分布范围则进一步扩大。 ACTβA与 TGF-β1 或α- SMA分布不同 ,βA主要分布在肝细胞 ,而 TGF-β1 或α- SMA以间质细胞 (肝星状细胞 )为主。结果表明肝纤维化时 ACTβA表达分布发生改变 。

To examine the changes in the expression and localization of Activin βA in the development of rat hepatic fibrosis induced by carbon tetrachloride (CCl 4), 74 male Sprague Dawley rats were randomly divided into a control group( n =10) and a model group( n =64) Hepatic fibrosis was induced in the model group by subcutaneous injection of 40% CCl 4 oil solution After CCl 4 injection for 1,2,3,4,5,6 and 7 weeks, 6～12 rats were killed each week, and the activin βA, TGF-β 1 and α-SMA expression and localization were examined by immunohistochemistry The examinations showed that the normal rat liver expressed activin βA More staining was found in the hepatocytes around the central veins After CCl 4 injection for 1 week, the range of activin βA immunostaining was contracted from the periphery of liver lobuli, but still restricted mainly around the central veins After CCl 4 injection for 2～3 weeks, activin βA immunostaining was decreased and became almost undetectable However, 4 weeks, injection caused an increase in βA immunostaining, and 5～7 weeks, injection enhanced it even further A great many hepatocytes around fibrotic areas (around portal tracts , fibrotic septa and central veins) were stained positive, even many hepatocytes in the inner part of pseudo lobule were stained Immunohistochemstry also showed that TGF β 1 or α SMA were localized in non parenchymal cells(hepatic stellate cells mainly) , while activin βA localized in parenchymal cells(hepatocytes) Considering the results above, it is concluded that activinβA may be involved in the pathogenesis of hepatic fibrosis.