茵甘合剂对ANIT诱导肝内胆汁淤积模型小鼠肝损伤防治作用及机制研究  

Protection effect of herba artemisiae and licorice mixture on mice model of ANIT-induced intrahepatic cholestatic and its mechanism

作　　者：张志荣[1] 张林林[1] 樊玉娟[1] 苏慧宗 李玥[1] 谭波[1] 蒋健[1] 裘福荣[1] 

机构地区：[1]上海中医药大学附属曙光医院临床药代动力学实验室,201203

出　　处：《肝脏》2017年第2期119-124,共6页Chinese Hepatology

基　　金：国家自然科学基金项目(81173118);上海市中医临床重点实验室项目(C10dZ2220200)

摘　　要：目的探讨茵甘合剂对α-萘异硫氰酸酯(ANIT)诱导肝内胆汁淤积模型小鼠肝损伤的作用。方法正常组、模型组、茵陈组、甘草组、茵甘合剂组,每组10只小鼠。正常组小鼠灌胃0.9%氯化钠溶液10 d,模型组、茵陈组、甘草组、茵甘合剂组小鼠分别灌胃0.9%氯化钠溶液(0.2 mL/20 g)、茵陈水煎液(1.13 g/kg)、甘草水煎液(1.13 g/kg)、茵甘合煎液(茵陈1.13 g/kg、甘草1.13 g/kg)10 d,在第7天给药后1 h灌胃ANIT(100 mg/kg)造模。第10天取血样,检测血清TBil、ALT、AST、ALP和TBA;肝病理检查;RT-PCR检测Car和Pxr及其下游靶基因转录情况。结果与模型组相比,茵甘合剂组小鼠肝脏损伤改善明显,血清TBil、ALT、AST、ALP和TBA水平分别降低22%、23%、25%、20%和30%;Car和Pxr及其下游靶基因CYP3a11、Ugt1a1、Sult2a1、Mdr2、Mrp2、Mrp3和Mrp4的mRNA的转录增加(P<0.01)。结论茵甘合剂对ANIT诱导的肝内胆汁淤积模型小鼠肝损伤具有防治作用。Objective To investigate the protective effect and mechanism of herba artemisiae and licorice mixture on mice model of intrahepatic cholestasis（IC）induced by alpha-naphthylisothiocyanate（ANIT）.Methods C57BL/6 female mice were randomly divided into normal group,model group,herba artemisiae group,licorice group and herba artemisiae/licorice mixture group,which were administrated with normal saline（0.2 mL/20 g）,herba artemisiae（1.13 g·kg^（-1）·d^（-1））,licorice（1.13 g·kg^（-1）·d^（-1））,herba artemisiae and licorice mixture（herba artemisiae 1.13 g·kg^（-1）·d^（-1） and licorice1.13 g·kg^（-1）·d^（-1））for 10 days,respectively.On day 7,all groups except normal group were additionally administrated with ANIT（100 mg/kg）.Serum levels of total bilirubin（TBil）,alanine aminotransferase（ALT）,aspartate transaminase（AST）,alkaline phosphatase（ALP）and total bile acid（TBA）were detected on day 10.Hepatic pathological examinations were observed by hematoxylin and eosin staining（HE）.Pregnane X receptor（Pxr）,constitutive androstane receptor（Car）and their target genes were quantitated by reverse transcription-polymerase chain reaction（RT-PCR）.Results Compared with those in model group,levels of TBil,ALT,AST,ALP and TBA in herba artemisiae/licorice mixture group were reduced by 22%,23%,25%,20% and 30%,respectively.Meanwhile,transcription levels of Pxr,Car,Ntcp,Oatp1,Bsep,Mdr2,Mrp2, Mrp3, Mrp4,Cyp3a11,Ugt1a1 and Sult2a1 were elevated（P〈0.01）.Conclusion Herba artemisiae/icorice mixture might have a certain protective effect on mice model of ANIT-induced IC.Mechanistically,it could activate nuclear receptors Pxr and Car,induce drug metabolism enzymes（Cyp3a11,Ugt1a1 and Sult2a1）and upregulate transporters expression（Bsep,Mrp2,Mrp3,Mrp4）,which promotes intrahepatic bile acid metabolism and reduces intrahepatic bile acids load.

关 键 词：茵甘合剂 肝内胆汁淤积 孕烷X受体 雄烷受体 胆汁酸 

分 类 号：R285.5[医药卫生—中药学] R-332[医药卫生—中医学]