荔枝核总黄酮对肝纤维化大鼠TGF-β1及Smad3、7表达的影响

Effect of total flavone of Litchi chinensis sonn on expression of TGF-β1,Smad3 and Smad7 of hepatic fibrosis in rats

目的探讨荔枝核总黄酮(TFL)对胆汁性肝纤维化大鼠肝组织转化生长因子β1(TGF-β1)、Smad3、7表达的影响及其抗肝纤维化可能的作用机制。方法将雄性SD大鼠70只随机分为假手术组、模型组、TFL大剂量组[200mg/(kg.d)]和TFL小剂量组[100mg/(kg.d)]。采用胆总管结扎制备肝纤维化大鼠模型。分别于术后第2、3、4周处死大鼠,留取肝脏组织。HE染色观察大鼠肝组织病理改变;免疫组织化学法检测TGF-β1、Smad3、7在肝组织内的动态表达。结果假手术组肝组织内TGF-β1、Smad3有少量表达,Smad7呈高表达。与模型组比较,TFL大剂量治疗后大鼠肝组织内纤维化程度降低。随着肝纤维化的形成和发展,第2、3、4周TFL大剂量组大鼠肝组织TGF-β1(3.000±1.309、2.000±1.309、1.800±1.649)、Smad3(2.875±1.458、2.000±1.309、1.833±0.753)与模型组TGF-β1(3.750±1.488、4.333±1.211、5.000±0.817)、Smad3(3.375±0.916、4.000±0.894、4.250±0.500)比较,差异有统计学意义(P<0.05)。结论 TFL能有效地减轻胆总管结扎所致肝纤维化大鼠肝损伤及肝纤维化程度,其机制可能与抑制TGF-β1、Smad3高表达,上调Smad7表达有关。

Objective To investigate the influence of total flavone（TFL）of Litchi Chinensis sonn on the expression of TGF-β1,Smad3 and Smad7 of hepatic fibrosis in rats,and to study the mechanism of TFL.Methods Seventy males SD rats were randomly divided into four groups：sham-operated group,model group,high-dose TFL group[200 mg/（kg·d）],low-dose group[100 mg/（kg·d）].The liver fibrosis model was prepared by bile duct ligation,where as the sham-operated group was used as controls.The rats were respectively killed at 2,3,4 weeks after operation.The liver histopathological changes were observed under light microscopy by HE staining.The expression and orientation of TGF-β1,Smad3 and Smad7 in hepatic fibrosis were detected by immunohistochemistry.Results TGF-β1 and Smad3 at 2,3,4 weeks in the sham-operated group were expressed in low amounts in the normal liver tissues,while Smad7 at the same points was decreased.Compared with the model group,the fibrotic degree of the liver tissues was reduced after high-dose TFL treatment.With the formation and development of fibrosis,the expression of TGF-β1 and Smad3 at 2,3 4 weeks were 3.000±1.309,2.000±1.309,1.800±1.649 and 2.875±1.458,2.000±1.309,1.833±0.753 respectively in the high-dose TFL group,while 3.750±1.488,4.333±1.211,5.000±0.817 and 3.375±0.916,4.000±0.894,4.250±0.500 respectively in the model group,showing statistical difference between the two groups（P0.05）.Conclusion TFL may effectively reduce the liver injury and hepatic fibrosis induced by common bile duct ligation.Its mechanism may inhibit the high expression of TGF-β1 and Smad3,and increase the expression of Smad7.