吡菲尼酮抑制TGF-β/Smad信号通路缓解四氯化碳诱导的小鼠肝硬化  

Pirfenidone inhibits TGF-β/Smad signaling pathway to alleviate hepatic cirrhosis induced by carbon tetrachloride

作　　者：冯雪[1] 李毅[1] 陈谭昇[1] 余永勤[1] 吕其军[1] FENG Xue;LI Yi;CHEN Tan-Sheng;YU Yong-Qin;L Qi-Jun(Infection Department of Shengli Oilfield Central Hospital,Dongying 257034,China)

机构地区：[1]胜利油田中心医院感染科,东营257034

出　　处：《中国免疫学杂志》2019年第2期161-164,共4页Chinese Journal of Immunology

摘　　要：目的:探究吡菲尼酮治疗四氯化碳诱导的小鼠肝硬化中的作用与机制。方法:60只C57BL/6雄性小鼠,随机分为空白组、模型组和低中高给药组,每组12只,小鼠腹腔注射20%CCl4大豆油溶液(5 ml/kg),每周2次,连续造模7周,自造模开始后第3周自由饮用20%乙醇水溶液。低中高剂量组分别按小鼠体重灌胃50、100和200 mg/kg的吡菲尼酮溶液,模型组和空白组分别灌胃给予相等体积的空白溶剂,造模结束后按照上述给药方式分组给药治疗,每天灌胃1次,治疗2周。比较分析治疗前后ALT、AST指标,小鼠肝脏指数、脾脏指数、TGF-β1和Smad3基因和蛋白表达水平。结果:模型组中小鼠血清ALT、AST含量显著上升(P<0. 05),吡菲尼酮灌胃治疗后3组小鼠血清ALT、AST含量显著下降(P<0. 05)。模型组与空白对照组相比肝脏、脾脏指数显著上升(P<0. 05),给药治疗后肝脾肿胀与模型组相比显著下降(P<0. 05)。模型组较空白组,其TGF-β1阳性细胞数目显著增多,给药后阳性细胞数目与模型组相比显著减少。Smad3基因表达水平比较,模型组比空白组显著升高(P<0. 05),各给药组小鼠肝脏组织TGF-β1和Smad3蛋白的基因水平较模型组相比显著下降(P<0. 05)。同时TGF-β1和Smad3蛋白的表达显著增高,给药后各组小鼠的TGF-β1和Smad3的表达有所下调。结论:吡菲尼酮能够通过抑制TGF-β/Smad信号通路关键TGF-β1、Smad3基因和蛋白表达缓解四氯化碳诱导的小鼠肝硬化。Objective:This research aimed to explore the therapeutic effect and its mechanism of pirfenidone in liver cirrhosis induced by carbon tetrachloride in mice.Methods:Sixty male C57BL/6 mice were randomly divided into the control group,model group and different doses of pirfenidone group,twelve rats in each group.Mice were intraperitoneally injected with 20% CCl4 soybean oil solution(5 ml/kg),twice a week for 7 weeks.And these mice were free to drink 20%ethanol solution in the third week after building the model.The low,medium and high dose groups were respectively given 50,100 and 200 mg/kg of pirfenidone solution according to the body weights,while the model group and control group were given equal volume of blank solvent after building the model,once a day for 2 weeks.The serum level of ALT and AST,liver index,spleen index,the gene or protein expression level of TGF-β1 and Smad3 were analyzed before and after the treatment of pirfenidone.Results:The serum level of ALT,AST increased significantly in the model group(P<0.05),while decreased significantly in different doses of pirfenidone group(P<0.05).The liver and spleen index in the model group was significantly higher than that in the control group(P<0.05).However,after treating with pirfenidone,the liver and spleen index were significantly lower than that in the model group(P<0.05).The number of TGF-β1 positive cells in the model group was significantly more than that in the control group,but it was significantly decreased in the pirfenidone group.The gene expression level of Smad3 in the model group was significantly higher than that in the control group(P<0.05).The gene expression level of TGF-β1 and Smad3 in different doses of pirfenidone group were significantly lower than that in the model group(P<0.05).Meanwhile,the protein level of TGF-β1 and Smad3 were significantly increased in the model group,while decreased in the pirfenidone group.Conclusion:Pirfenidone relieves liver cirrhosis caused by carbon tetrachloride in mice by inhibiting the TGF-β1/Smad

关 键 词：吡菲尼酮 TGF-Β/SMAD信号通路 肝硬化 四氯化碳 

分 类 号：R657.3[医药卫生—外科学]