藤茶总黄酮调控TGF-β1/Smad信号通路抗肝纤维化机制的研究  

Mechanism of tengcha flavonoids on anti-hepatic fibrosis by regulating TGF-β1/Smad signaling pathway

作　　者：张文涛[1] 吴先昊 梁冰洁 甘彩玉 郑作文[1] ZHANG Wentao;WU Xianhao;LIANG Bingjie;GAN Caiyu;ZHENG Zuowen(Pharmacology Department,Guangxi University of Chinese Medicine,Nanning,Guangxi 530200,China;Pharmacology Department of Chinese Medicine,Chinese Medicine Research Institute ofJiangxi Province,Nanchang,Jiangxi 330046,China)

机构地区：[1]广西中医药大学药理教研室,南宁530200 [2]江西省中医药研究院中药药理室,南昌330046

出　　处：《重庆医学》2019年第9期1493-1499,共7页Chongqing medicine

基　　金：广西中药药效研究重点实验室资助项目(16-380-29);广西科技创新平台建设示范专项(KJT16022)

摘　　要：目的探讨藤茶总黄酮(TF)通过调控转化生长因子β1(TGF-β1)/Smad信号通路抗小鼠肝纤维化的机制。方法将98只昆明小鼠(雌雄兼用)分为对照组、模型组、秋水仙碱组(0.2mg/kg),TF高、中、低剂量组(300、150、75mg/kg),其中模型组28只(因实验过程中会有死亡),其余各组每组14只。除对照组外,给予各组小鼠背部皮下注射25%四氯化碳(CCl4)花生油溶液,每3天1次,连续10周,造成小鼠肝纤维化模型,对照组背部皮下注射等量100%花生油溶液(每3天1次,连续10周);造模同时,除对照组和模型组小鼠给予蒸馏水灌胃外,其余各组小鼠给予相应药物灌胃给药,每天1次,连续10周。第10周末,摘眼球取血,处死小鼠取肝组织。生化分析法检测各组小鼠血清丙氨酸氨基转移酶(ALT)及天冬氨酸氨基转移酶(AST)水平。ELISA法检测肝组织中Ⅰ型胶原蛋白(ColⅠ)、Ⅲ型胶原蛋白(ColⅢ)及TGF-β1的水平。制作肝组织切片HE染色,免疫组织化学法检测肝组织TGF-β1/Smad信号通路中主要蛋白的表达。结果与模型组比较,TF高、中、低剂量组肝纤维化小鼠血清ALT、AST水平和肝组织ColⅠ、ColⅢ水平明显降低(P<0.05);给药各组小鼠肝组织炎症、坏死现象明显减轻,胶原蛋白增生情况改善。结论 TF可通过调节TGF-β1/Smad信号通路中主要蛋白的表达,从而达到抗肝纤维化的作用。Objective To explore the mechanism of tengcha flavonoids(TF)on anti-hepatic fibrosis by regulating TGF-β1/Smad signaling pathway.Methods 98 Kunming mice(including male and female)were divided into the control group,the model group,the colchicine group(0.2 mg/kg),the TF high-,middle-,lowdose groups(300,150,75 mg/kg)with 14 mice in each group except 28 mice in the model group.Mice were given hypodermic 25% CCl4 peanut oil once every 3 dfor 10 weeks to establish hepatic fibrosis models except for the control group.At the same time,mice were given distilled water by intragastric administration in the control group and the model group,and corresponding drugs once a day for 10 weeks in other groups.At the end of week 10,the levels of ALT,AST in serum were detected by biochemical analysis.CollagenⅠ(ColⅠ),CollagenⅢ(ColⅢ)in liver were detected by ELISA method.The expression of the major proteins in TGF-β1/Smad signaling pathway in liver tissues was determined by immunohistochemistry.Results Comparing with the model group,TF can obviously reduce the serum ALT,AST and ColⅠ,ColⅢin liver tissue in mice with liver fibrosis(P<0.05).The inflammation and necrosis of liver tissue significantly reduced,and collagen hyperplasia improved in the TF group.Conclusion TF plays an anti-fibrosis role by regulating the expression of the major proteins in TGF-β1/Smad signaling pathway.

关 键 词：转化生长因子Β1 肝硬化 藤茶总黄酮 

分 类 号：R285.5[医药卫生—中药学]