茵陈术附汤抑制TLR4/NF-κB通路对α-萘异硫氰酸酯诱导肝内胆汁淤积症模型小鼠肝损伤的保护作用  

Hepatoprotective effects of Yinchenzhufu decoction on intrahepatic cholestasis liver injury in mice induced by ANIT via suppressing TLR4/NF-κB pathway

作　　者：王倩[1] 苏慧宗 李玥[1] 谭波[1] 严东明 金静怡 裘福荣[1] WANG Qian;SU Huizong;LI Yue;TAN Bo;YAN Dongming;JIN Jingyi;QIU Furong(Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学附属曙光医院,上海201203

出　　处：《中国临床药理学与治疗学》2020年第6期601-609,共9页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金项目(81874346);上海市中医临床重点实验室项目(C14dZ2273200)。

摘　　要：目的:基于肝细胞Toll样受体4/核因子kappa B(toll-like receptor 4/nuclear factor kappa B,TLR4/NF-κB)通路探讨茵陈术附汤对α-萘异硫氰酸酯(ANIT)所致肝内胆汁淤积模型小鼠肝损伤保护作用。方法:C57BL/6雄性小鼠灌胃茵陈术附汤,每天一次,连续10 d,于第7天灌胃75mg/kg ANIT油溶液造模,于第11天上午采集血液和肝脏样本。测定血生化、肝脏病理、肝脏中胆汁酸含量的变化及TLR4/NF-κB通路中相关蛋白表达量。结果:与模型组相比,茵陈术附汤组肝脏坏死明显好转,炎性细胞浸润有所减少;血浆谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(ALP)、总胆汁酸(TBA)和总胆红素(TBIL)明显下降,肝脏胆汁酸胆酸(CA)、β-鼠胆酸(β-muri-cholic acid,β-MCA)、牛磺胆酸(TCA)、牛磺熊去氧胆酸(TUDCA)和牛磺鹅去氧胆酸(TCDCA)含量显著减少;Western blot测定的TLR4和p-NF-κB p65的蛋白表达量显著下降;ELISA检测IL-1β、IL-6、TNF-α和单核细胞趋化蛋白-1(MCP-1)等细胞因子水平明显降低。结论:茵陈术附汤对ANIT诱导的小鼠肝内胆汁淤积肝损伤有保护作用,其机制可能与其减少肝内胆汁酸淤积,抑制TLR4/NF-κB通路和抑制炎症反应有关。AIM:To investigate the hepatoprotective effects of Yinchenzhufu decoction(YCZFD)via TLR4/NF-κB pathway on the hepatic injury in alpha-naphthyisothiocyanate(ANIT)-induced intrahepatic cholestasis mice.METHODS:Male C57BL/6 mice were administered with YCZFD for consecutive 10 days,and intrahepatic cholestasis mice model was induced by orally given ANIT at dose of 75 g/kg on the seventh day.On the last day,the blood samples and liver samples were collected 2 hours after oral administration of YCZFD.The serum biochemical index,liver histopathology,the change of bile acid contents in mice liver,and the expression of relative proteins in TLR4/NF-κB pathway were determined.RESULTS:Compared with the model group,YCZFD treatment group significantly improved the hepatic necrosis and reduced the inflammatory cell infiltration.The plasma alanine aminotransferase(ALT)and aspartate aminotransferase(AST),alkaline phosphatase(ALP),total bile acid(TBA),and total bilirubin(TBIL)levels were significantly decreased,and the free and conjugated bile acids were both reduced.The expression of TLR4,IL-1β,IL-6,TNF-α,and MCP-1 were significantly decreased.CONCLUSION:YCZFD presents hepatoprotective effects on the hepatic injury in ANIT-induced intrahepatic cholestasis mice,which may be related to inhibiting the TLR4/NF-κB pathway,reducing the intrahepatic bile acids,and suppressing the inflammatory reaction.

关 键 词：胆汁淤积性肝损伤 TLR4/NF-κB通路 茵陈术附汤 

分 类 号：R965.2[医药卫生—药理学]