维生素E对肝纤维化大鼠金属蛋白酶组织抑制因子-2、Ⅲ型胶原及纤维连接蛋白表达的影响

Influences of vitamin E on the expression of tissue inhibitor of metalloproteinase-2, type Ⅲ collagen and fibronectin in CCL_4-induced rats liver fibrosis.

目的 研究维生素E(VE)防治肝纤维化作用及可能存在的机制。方法 以四氯化碳制备大鼠肝纤维化模型 ,用VE乳剂 (10 0mg/kg ,2次 /周 )静脉注射 ,连续 10周。免疫组织化学检测肝组织Ⅲ型胶原、纤维连接蛋白 (FN)沉积 ;原位杂交检测肝内金属蛋白酶组织抑制因子 2 (TIMP 2 )及α1(Ⅲ )前胶原mRNA表达。结果 治疗组大鼠肝内Ⅲ型胶原蛋白及FN形成较对照组减少 ;α1(Ⅲ )前胶原及TIMP 2mRNA表达降低 ,经图像分析 ,与对照组差异有显著性 (P<0 .0 5 )。结论 VE治疗可下调肝纤维化大鼠TIMP 2基因表达 ,减少细胞外基质沉积 。

Objective To study the influences of vitamin E(VE) on liver fibrosis and its mechanism of action. Methods Liver fibrosis was induced in rats by the administration of CCL 4. The treatment group was treated with VE(100 mg/kg, IV) twice a week for 10 weeks after the liver fibrosis model was established. Immunohistochemical staining of hepatic type Ⅲ collagen protein and fibronectin were carried out in the 10th week after the administration of VE. At the same time, the hepatic contents of α 1(Ⅲ) procollagen and tissue inhibitor of metalloproteinase 2(TIMP 2)mRNA were observed with in situ hybridiznion. Results There were much less type Ⅲ collagen protein and fibronectin in the liver in the group treated with VE than that in the control. The expression of TIMP 2 and α 1(Ⅲ) procollagen mRNA were significantly inhibited in the treatment group. These changes were statistically significant as compared with that of the control group as examined by an image analysis system( P <0.05)。 Conclusion VE treatment can down modulate the expression of TIMP 2 mRNA in rats with liver fibrosis, thereby, play a role in the attenuation of fibrosis.