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

Abstract: 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 licorice 1.13 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.

Key words: Herba artemisiae and licorice mixture, Intrahepatic cholestasis, Pregnane X receptor, Constitutive androstane receptor, Bile acid