摘要
目的 观察四氯化碳 (CCl4 )诱导实验性肝纤维化模型大鼠肝纤维化形成过程中激活素(activin ,ACT)A的表达。方法 40 %CCl4 皮下注射制备大鼠实验性肝纤维化模型 ,注射CCl4 1、2、3、4、5、6及 7周后分批处死动物 ,每次 6~ 10只 ,采用半定量逆转录聚合酶链反应 (RT PCR)及免疫组化法检测ACTβA亚基mRNA和蛋白质的表达。 结果 RT PCR和免疫组化研究表明 ,正常肝脏表达ACTβA亚基 ,但在肝纤维化形成过程中其表达一过性下降到检测不出的水平 (注射CCl4 后 2、3周 ) ,然后又逐渐升高 ,注射 6、7周后显著高于正常动物 (P <0 .0 1) ,其mRNA表达水平分别为正常大鼠的 1.6和 2 .2倍。免疫组化研究还表明 ,正常时ACTA表达主要位于肝小叶内的肝细胞 ,在肝纤维化形成后表达显著增加 ,分布发生改变 ,纤维化区域周围有大量表达ACT的肝细胞存在。结论 ACTA可能在后期参与了肝纤维化的形成。
Objective Activin A, a member of the transforming growth factor (TGF β) superfamily, has been reported to overexpress in liver cirrhosis. The aim of this study was to examine the expression changes of activin A in the process of carbon tetrachloride induced rat hepatic fibrosis. Methods Hepatic fibrosis was induced in rats by subcutaneous injections of 40% carbon tetrachloride oily solution for a period of 1 to 7 weeks. 6~10 rats were killed at week 1,2,3,4,5,6 and 7 weeks. The kinetics of activin A messenger RNA expression and its protein localization were assayed by semi quantity reverse transcription polymerase chain reaction (RT PCR) and immunohistochemistry. Results RT PCR and immunohistochemistry showed normal rat liver could express activin A mRNA and protein, and its expression was transiently decreased and became undectable after carbon tetrachloride injections for 2 or 3 weeks, then increased grandually. After carbon tetrachloride injecting for 6 and 7 weeks, activin A mRNA and protein expression were significantly enhanced in rats liver ( P <0.01). Compared with normal rats liver, activin A mRNA expression level was 1.6 and 2.1 fold elevated in rats liver with carbon tetrachloride injections for 6 and 7 weeks. Immunohistochemistry showed activin A expressed in hepatocytes of normal liver, and its expression became decreased in rats injecting carbon tetrachloride injections for 2 or 3 weeks. Compared with normal liver, activin A expression distribution pattern changed in fibrotic liver. Activin A expression was increased significantly in hepatocytes around fibrotic areas. Conclusions Activin A expression was increased in later stage of hepatic fibrotic process, and may involve in hepatic fibrosis formation in this stage.
出处
《中华消化杂志》
CAS
CSCD
北大核心
2001年第6期346-348,共3页
Chinese Journal of Digestion