TGF-β Ⅲ型受体在小鼠肝纤维化中的作用研究

摘要

Objective To investigate effects of type Ⅲ TGF-β receptor(TβRⅢ) on carbon tetrachloride(CCl4)-induced hepatic fibrosis in mice.Methods C57BL/6J mice were randomly divided into normal control group and CCl4-induced liver fibrosis model group.Mice in model group were treated twice weekly with i.p.injections of 5 ml/kg CCl4 diluted in nine volumes of oil for 8 weeks.Mice were sacrificed at 2, 4, 6, 8 weeks.The liver histopathological change was examined by HE staining.Serum transaminase(ALT, AST) activities were detected by commercial kit.The expressions of collagen Ⅰ, TβRⅢ, p-Smad3, Smad3, p-Akt, Akt in the liver were measured by Western blot.Results The results of HE staining showed that the liver fibrosis gradually increased with the prolongation of time, as well as serum ALT and AST activities.Western blot showed that the collagen Ⅰ expression was gradually increased, TβRⅢ expression was decreased with the aggravation of hepatic fibrosis.Moreover, TβRⅢ expression was negatively correlated with the collagen Ⅰ expression.Furthermore, p-Smad3, p-Akt expression in liver tissues were gradually increased.Conclusion The decrease of TβRⅢ may associates with the development of hepatic fibrosis.%目的 建立四氯化碳(CCl4)诱导的肝纤维化小鼠模型,观察转化生长因子β Ⅲ型受体(TβRⅢ)在肝纤维化中的作用.方法 C57BL/6J小鼠随机分为正常对照组和CCl4模型组,模型组腹腔注射10% CCl4油溶液(5 ml/kg),每周2次,分别在造模第2、4、6、8周处死小鼠,HE染色观察小鼠肝脏的病理学变化,检测模型进展过程中血清谷丙转氨酶(ALT)、谷草转氨酶(AST)活性,Western blot法检测肝组织中I型胶原、TβRⅢ、p-Smad3、Smad3、p-Akt、Akt的表达情况.结果 HE染色结果显示,随着造模时间的延长,小鼠肝纤维化程度逐渐加重,血清ALT、AST活性逐渐增加,Western blot 结果显示I型胶原的表达逐渐增加,TβRⅢ的表达逐步降低,p-Smad3和p-Akt的表达逐渐升高.结论 TβRⅢ的降低可能与小鼠肝纤维化的发生发展有关.