荔枝核总黄酮防治胆汁淤积性大鼠肝纤维化的实验研究

Total flavone of Litchi Chinensis Sonn suppressing hepatic fibrosis caused by bile duct ligation in rats

目的探讨荔枝核总黄酮(TFL)对胆汁淤积性大鼠肝纤维化的防治作用及其机制。方法雄性SD大鼠80只,随机分为假手术组、模型组、TFL大剂量组[200 mg/(kg.d)]、TFL小剂量组[100 mg/(kg.d)],每组20只。采用胆总管结扎制备肝纤维化大鼠模型,于术后第4周时处死大鼠,留取大鼠肝左叶组织,HE染色观察肝纤维化程度变化;免疫组化方法检测转化生长因子-β1(TGF-β1)和Smad3、Smad7蛋白的表达。结果术后第4周,与模型组比较TFL大剂量组肝小叶结构破坏明显减轻,肝纤维化程度较模型组明显好转,与假手术组结构接近;TFL小剂量组肝小叶结构破坏程度和肝纤维化程度介于模型组与TFL大剂量组之间。TFL大剂量组肝组织中TGF-β1、Smad3表达明显减少,Smad7表达显著增高;TFL小剂量组TGF-β1和Smad3、Smad7蛋白表达与模型组比较无明显差异(P>0.05)。结论 TFL能有效减轻胆汁淤积性肝纤维化大鼠肝损伤及肝纤维化程度,其机制可能与调控TGF-β1、Smad3/7信号转导表达有关。

Objective To investigate the effects of treatment with total flavone of Litchi Chinensis Sonn （TFL） on the expression of TGF-β1 and Smad3/7 in experimental hepatic fibrosis in rats, and to explore its anti-fibrotic mechanism. Methods Eighty male 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） ]. Liver fibrosis model was prepared by bile duct ligation, whereas the sham-operated group was used as controls. The rats were killed at 4 weeks after operation. The liver histopatho- logical changes were observed under light microscopy by HE staining. The expression and orientation of TGF-β1, Smad3 and Smad7 in hapatic fibrosis were detected by immunohistochemistry. Results At the 4th week after operation, the structure of high-dose TFL group was almost restored to normal; hepatic fibrosis score was obviously redueed. The protein expression of TGF-β1, Smad3 were remarkably down-regulated, and Smad7 was significantly up-regulated compared with model group. Low-dose group was no significant difference compared with model group. Conclusion TFL can reverse hepatic fibrosis by controling the protein repression of TGF-β1 and Smad3/7.