This paper aimed to investigate the protective effect and mechanism of the Tibetan medicine Ershiwuwei Songshi Pills on α-naphthalene isothiocyanate(ANIT)-induced cholestatic liver injury in rats based on the farnesol X receptor(FXR) signaling pathway. SD rats were randomly divided into blank group, model group, ursodeoxycholic acid(UDCA) group, Tibetan medicine Ershiwuwei Songshi Pills low, medium and high dose groups(0.09, 0.18, 0.36 g·kg~(-1)). A prophylactic dosing regimen was used in the experiment. From the 1 st to 4 th days, the UDCA group and the Tibetan medicine Ershiwuwei Songshi Pills suspension groups received prophylactic gavage administration; on the 5 th day, the blank control group was given an equal volume of olive oil blank reagent, and the remaining groups were given ANIT modeling reagent. Administration was continued on day 5 to 6 in each administration group. Forty-eight hours after modeling on the 7 th day, blood was collected from the femoral artery of rats. Serum alkaline phosphatase(ALP), alanine aminotransferase(ALT), aspartate aminotransferase(AST), direct bilirubin(DBIL), total bilirubin(TBIL), and total bile acid(TBA) levels were detected, and liver histopathological changes were observed. The relative expression changes of FXR, SHP, CYP7 A1, MRP2, MRP3, NTCP, BSEP mRNA in liver tissues were detected by Real-time fluorescence quantitative method, and the expression changes of FXR, SHP, UGT2 B4 protein in liver tissues were detected by Western blot. The results showed that the Tibetan medicine Ershiwuwei Songshi Pills significantly reduced the levels of ALT, ALP, DBIL, TBIL and TBA in the serum of the ANIT mo-del rats(P<0.01, P<0.05), significantly up-regulated the mRNA expressions of SHP and NTCP(P<0.01, P<0.05), significantly down-regulated the mRNA expression of CYP7 A1 and MRP3(P<0.01, P<0.05); and significantly up-regulated the protein expressions of FXR and SHP(P<0.01, P<0.05). The Tibetan medicine Ershiwuwei Songshi Pills have an obvious protective effect on ANIT-induced cholestatic liver injury in rats, and its mechanism may be related to the bile acid metabolism mediated by the FXR signaling pathway.
Keywords: Ershiwuwei Songshi Pills; cholestasis; farnesol X receptor(FXR); liver injury; α-naphthalene isothiocyanate(ANIT).