水飞蓟素对肝纤维化小鼠的保护作用及机制探讨  

The effect and mechanism of Silymarin on liver fibrosis in mice

作　　者：曹力波[1,2] 李兵[2] 李佐军[2] 黄娟娟[1,2] 欧阳林旗[1,2] 黄瀚[1,2] 刘世坤[2] 

机构地区：[1]中南大学药学院,湖南长沙410013 [2]中南大学湘雅三医院药剂科,湖南长沙410013

出　　处：《中国药理学通报》2009年第6期794-796,共3页Chinese Pharmacological Bulletin

基　　金：湖南省自然科学基金资助项目(No2008SK3067)

摘　　要：目的探讨水飞蓟素抗CCl4和酒精所致肝纤维化的作用和机制。方法50只♂昆明小鼠随机分为5组,模型组小鼠皮下注射CCl4并饮用酒精制造肝纤维化模型,治疗组以低、中、高3种不同浓度(50、100、200mg.kg-1)的水飞蓟素灌胃进行干预,正常组小鼠皮下注射等量植物油并用生理盐水灌胃。通过检测血清AST、ALT水平、肝脏病理组织学变化、肝脏组织转化生长因子-β1(TGF-β1)、α-肌动蛋白(α-SMA)及Ⅰ型胶原(collagen-Ⅰ)mRNA表达水平观察水飞蓟素的疗效。结果成功建立肝纤维化模型,模型组小鼠血清AST、ALT,肝脏组织TGF-β1、α-SMA及collagen-ⅠmR-NA表达水平增高,水飞蓟素可降低血清AST、ALT水平,降低肝组织TGF-β1、α-SMA及collagen-ⅠmRNA的表达,减轻肝纤维化程度,中剂量(100mg.kg-1)疗效最好。结论水飞蓟素对酒精和CCl4所致的肝脏损伤有明显保护作用,其机制可能与降低TGF-β1mRNA的表达、抑制肝星状细胞(hepatic stellate cells,HSC)活化有关。Aim To observe the anti-fibrosis effect and mechanism of Silymarin （SIL） on mice hepatic fibrosis caused by alcohol and CCl4. Methods 50 Kunming mice were randomly divided into 5 groups. Fibrosis model group was given CCl4 through subcutaneous injections plus alcohol oral administration. The treated groups were divided into low dose （50 mg.kg^-1 body weight）, medium dose （100mg.kg^-1 body weight）, high dose （200mg.kg^-1 body weight） of SIL and normal group was given plant oil through subcutaneous injections and physiological saline oral administration. All groups were raised for 8 weeks. ALT and AST of serum, the histopathology of the mice liver and the mRNA expression of TGF-β1, α-SMA and collagen- I were detected. Results The hepatic fibrosis mice models were successfully made, the level of serum AST, ALT and TGF-β1 ,α-SMA and collagen-I mRNA of liver were increased in model groups, SIL decreased the level of serum ALT, AST and the expression of TGF-β1, α-SMA and collagen- I mRNA, the medium dose of SIL had the most significant effect. Conclusion SIL significantly reduces alcohol and CC14-induced mice hepatic fibrosis, probably by reducing the expression of TGF-β1 mRNA and then inhibiting the proliferation of HSC.

关 键 词：肝纤维化 水飞蓟素 转化生长因子-Β1 Α-肌动蛋白 Ⅰ型胶原 

分 类 号：R-332[医药卫生] R282.71