罗格列酮影响肝纤维化大鼠转化生长因子β_1(TGF-β_1)表达的机制

Effects of rosiglitazone on the expression of TGF-β_1 in experimental hepatic fibrosis rats

目的探讨罗格列酮对大鼠肝纤维化的保护作用和对转化生长因子β1(TGF_β1)mRNA表达影响的机制。方法检测肝组织病理学改变;生化法检测肝功能指标;免疫组织化学技术检测TGF_β1、PPARγ在肝内的表达及定位;采用RT_PCR检测肝组织TGF_β1、PPARγmRNA的表达。结果与模型组大鼠比较,干预组肝组织结构变化明显改善,纤维化增生程度减低,肝功能改善,大鼠肝内TGF_β1表达有所降低,并且大剂量组干预效果最为显著。结论罗格列酮能有效减轻肝纤维化大鼠的肝脏损伤及纤维化程度,其机制可能与PPARγ直接或间接抑制肝内TGF_β1mRNA的表达有关。

Objective To investigate the effects of Rosiglitazone（RGZ） on the expression of transforming growth factor β1 （TGF-β1） in experimental liver fibrosis in rats. Methods Sixty SD rats（liver fibrosis model was induced by CCl4 administration） were randomly divided into 6 groups, a normal control group, a model group, a RGZ group, and interventional groups （low dosage, medium dosage, high dosage）. The RGZ interventional groups were treated with RGZ once a day. At the end of the 8th week ,all rats were sacrificed and liver tissue specimens were used for histopathological examination（ HE, Massen and Gordon-Sweet）. Blood samples were collected for determination of ALT, AST and ALB. The effects of RGZ were evaluated by the expression of TGF-β1 and PPAR γ in liver tissue through immunohistochemical staining and RT-PCR. Results The liver fibrosis degree and the content of TGF-β1 in liver were significantly reduced in RGZ interventional groups compared with the model group. The levels of ALT and AST were significantly decreased, and ALB was increased in interventional groups compared with the model group（ P 〈 0.01）.And the expression of PPAR γ mRNA increased significantly in RGZ groups（ dose dependent）. Conclusion RGZ has protective effect on experimental hepatic fibrosis rats. The mechanism is possibly that PPAR γ has inhibitory effect on the expression of TGF-β1.