牛磺酸、表没食子儿茶素没食子酸酯和三羟基异黄酮联合用药对肝纤维化大鼠的治疗作用及机制  

Therapeutic Effects and Mechanisms of Combined Therapy of Taurine,Epigallocatechin Gallate,and Genistein on Liver Fibrosis in Rats

作　　者：曹雯[1] 廖明[2] 周燕[1] 林兴[2] 

机构地区：[1]广西医科大学药学院,南宁530021 [2]广西医科大学医学科学实验中心区域性高发肿瘤早期防治研究重点实验室,南宁530021

出　　处：《中国实验方剂学杂志》2015年第4期107-111,共5页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81160063);广西自然科学基金项目(2013GXNSFBA019167);广西区域性高发肿瘤早期防治研究重点实验室基金(GK2013-13-A-01-03)

摘　　要：目的:以表没食子儿茶素没食子酸酯(EGCG),牛磺酸和三羟基异黄酮3种具有不同抗纤维化作用的药物组成联合用药,研究其对肝纤维化大鼠的治疗作用及机制。方法:将SD大鼠分为正常组(n=10),模型组(n=12),秋水仙碱组(1 mg·kg-1,n=12),联合用药低剂量62.5 mg·kg-1组(牛磺酸50 mg·kg-1+EGCG 7.5 mg·kg-1+三羟基异黄酮5 mg·kg-1,n=12),中剂量125 mg·kg-1组(牛磺酸100 mg·kg-1+EGCG 15 mg·kg-1+三羟基异黄酮10 mg·kg-1,n=12)、高剂量250mg·kg-1组(牛磺酸200 mg·kg-1+EGCG 30 mg·kg-1+三羟基异黄酮20 mg·kg-1,n=12),除正常组外,其余各组大鼠分别ig50%四氯化碳(CCl4)溶液,正常组给予花生油,连续14周。于第9周开始各给药组分别ig给予相应的药物,连续6周。末次ig后处死动物,采集大鼠血清和肝组织标本,测定血清中丙氨酸转氨酶(ALT),天冬氨酸转氨酶(AST),转化生长因子β1(TGF-β1),Ⅰ型胶原(collagen I)的含量及肝组织中总抗氧化能力(T-AOC),超氧化物岐化酶(SOD),谷胱甘肽过氧化酶(GSHPx)的含量,HE染色观察肝组织病理变化。结果:与正常组相比,模型组大鼠血清ALT,AST,TGF-β1和collagen I含量升高(P<0.05),肝组织中T-AOC,SOD和GSH-Px含量降低(P<0.05);与模型组相比,联合用药中、高剂量组能降低肝纤维化大鼠血清中ALT,AST,TGF-β1和collagen I的生成(P<0.05),而联合用药高剂量组能升高肝组织中T-AOC,SOD和GSH-Px的含量(P<0.05)。结论:联合用药能有效对抗CCl4诱导大鼠肝纤维化并对肝脏起保护作用,其机制可能与加快自由基清除,减轻脂质过氧化损伤,同时抑制TGF-β1的表达,减少细胞外基质的合成有关。Objective ： To investigate the effect of combined therapy of epigallocatechin gallate, taurine,and genistein on CCl4-induced liver fibrosis in rats and its mechanism. Method： The SD rats were divided into six groups randomly： normal group （n = 10）, model group （n = 12） , colchicine group （1mg·kg^-1, n = 12） , combination therapy low [tauriue 50mg·kg^-1 ＋ epigallocatechin gallate （EGCG） 7.5 mg·kg^-1 ＋ genistein 5 mg·kg^-1, n=12], middle （taurine 100 mg·kg^-1 ＋EGCG 15 mg·kg^-1 ＋genistein 10 mg·kg^-1, n =12） and high （taurine 200 mg·kg^-1 ＋EGCG 30 mg·kg^-1 ＋ genistein 20 mg·kg^-1, n=12） dose group. The rats except normal group were induced by intragastric administration （ig） of 50% CCl4 for lg weeks, and the normal group was given peanut oil. Treatment was started at the 9th week for 6 weeks. Rats were sacrificed after the last administration, and the serum and liver tissue were taken quickly. The levels of alanine amino aspartate aminotransferase （AST）, transforming growth factor β1（TGF-β1） and collagen I antioxidamt capacity （T-AOC）, superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） activities in liver were measured, and HE staining was performed to evaluate histopathologic changes. Result： Compared with normal group, levels of ALT, AST, TGF-β1 and collagen I increased and liver T-AOC, SOD and GSH-Px activities decreased significantly in the model group （P 〈 0.05）. Compared with the model group, levels of ALT, AST, TGF-β1 and collagen I decreased significantly in combined therapy of middle and high dose group, and liver T- AOC, SOD and GSH-Px activities increased significantly in combined therapy of high dose group （P 〈 0.05 ）. Conclusion： Combined therapy has certain curative effect on CC14-induced liver fibrosis in rats. Its mechanism may involve scavenging free radical, alleviating the lipid peroxidation, inhibiting the expression of TGF-β1 and reducing the synthesis of extracellular matrix.

关 键 词：联合用药 表没食子儿茶素没食子酸酯 牛磺酸 三羟基异黄酮 肝纤维化 

分 类 号：R285.5[医药卫生—中药学]