肝纤维化大鼠转化生长因子β1／Smad蛋白的动态表达及意义

目的探讨转化生长因子TGF—β1／Smad信号通路在实验性肝纤维化发生中的作用。方法50只健康雄性SD大鼠分为2组：正常组和模型组,模型组大鼠利用40％CCl4油剂诱导形成肝纤维化模型,于6周及9周观测肝标本的病理,免疫组化法检测肝组织TGF—β1／Smad蛋白表达。结果①肝组织病理：与正常组比较,模型组大鼠肝组织都有不同程度的炎症和纤维化产生。模型组纤维化程度较正常对照组明显,差异有统计学意义（P〈0．05）;②TGF—β1／Smad基因蛋白：免疫组织化学检测显示,与正常对照组相比,模型组大鼠肝脏中TGF—β1、转化生长因子βI型受体（TβR—I）、Smad2、3、Smad,蛋白表达均显著增强（P〈0．01）,模型组大鼠肝脏TGF—β1、TβR-I、Smad。和Smad,之间存在正相关关系（P〈0．05或0．01）;模型组大鼠肝脏纤维化分级与TGF—β1、TβR—I、Smad2/3和Smad,之间存在正相关关系（P〈0．05或0．01）。结论肝组织TGF—β1／Smad蛋白表达水平与肝纤维化程度相关,TGF-β1／Smad信号的增强可能促进了肝纤维化的进展。

Dynamic expression of TGF-beta1/Smad protein in CCl4-induced liver fibrosis and its significance in rats

Objective To investigate the dynamic expression of TGF-β1/Smad protein in rats with liver fibrosis induced by carbon tetrachloride（ CCl4 ） ,to study mechanism of TGF-β1/Smad signaling and the relationship between its transduction and liver fibrosis. Methods Fifty healthy male SD rats were randomly divided into two groups： normal control group and model group. Experimental liver fibrosis was induced by subcutaneous injection of CCl4. After six weeks and nine weeks, histnpathological changes and degrees of fibrosis were observed by optical microscopy. Meanwhile, the expression of TGF-β1 , TβR- I , Smad2/3 and Smad7 proteins was detected by immunohistochemistry. Results （1） Pathological observation of hepatic specimens： hepatic tissue of model group rat had inflammation and fibrosis in different degrees. By comparing with the degrees of inflammation and fibrosis model groups were more severe than normal control group （P 〈 0.05 ）. （2） Changes of protein levels about TGF-β1/Smad： the expressions of TGF-β1 ,TβR- I , Smad2/3 and Smad7 in rat hepatic tissue were detected with immunohistochemistry techniques. The expressions of the four items in model group were higher than those of normal control group（ P 〈 0. 01 ）. In fibrosis model group, there exist considerable positive correlations among expressions of TGF-β1 ,TβR- ] , Smad2/3, Smad7 and degrees of fibrosis in livers（P 〈 0. 05 or 0.01 ）. Conclusion There is close relation between the level of TGF-[31 ,TβR- I ,Smad2/3 ,Smad7 and the different liver fibrosis grades due to CCl4. The up regulation of TGF-β1 ,TβR- I ,Smad2/3 and Smad7 in liver tissue is involved in the progression of hepatic fibrosis.