Mechanism of sarmentosin on juvenile intrahepatic cholestasis in rats

To study the effects of sarmentosin(SA)on the intervention and regulation of juvenile intrahepatic cholestasis in rats, 48 young SD rats were randomly divided into the control group, α-naphthylisothiocyanate(ANIT)model group, ursodeoxycholic acid(UDCA)positive control group and low-, medium- and high- dosage groups of SA, with 8 rats in each group. Except for the control group, rats in each group were given corresponding drugs by gavage once a day for a week, and 80 mg/kg ANIT model was established on the 5th day. Bile excretion was measured 48 hours after the establishment of the model; the activities of alanine aminotransferase(ALT), aspartate aminotransferase(AST)and alkaline phosphatase(ALP)and the contents of total bilirubin(TBIL), direct bilirubin(DBIL)and total bile acid(TBA)in serum were measured. The pathological changes of liver tissue and the contents of malondialdehyde(MDA), superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)in tissue homogenate were detected, and the expressions of tumor necrosis factor-α(TNF-α), γ-interferon(IFN-γ)and interleukin-1β(IL-1β)in serum were determined. Bile acid transporters and synthetic proteins were analyzed by Western blot. Compared with the control group, bile excretion was significantly inhibited in the model group; liver tissue showed obvious pathological damage; serum levels of ALT, AST, ALP, TBIL, DBIL and TBA were significantly increased; MDA content in tissue homogenate was significantly increased, SOD and GSH-Px contents were significantly decreased; inflammatory factors TNF-α, IFN-γ and IL-1β were significantly decreased in the model group. The expression of FXR, SHP-1, SHP-2, MREP2, BSEP and NTCP decreased, while the expression of CYP7A1 and CYP27A1 increased. Compared with the model group, the bile excretion of rats in each dose of SA group increased in varying degrees; the pathological damage of liver tissue was improved; the levels of ALT, AST, ALP, TBIL, DBIL and TBA in serum were decreased; the contents of MDA in liver homogenate were decreased; and the contents of SOD and GSH-Px were increased; the expression of TNF-α, IFN-γ and IL-1β decreased. The results showed that sarmentosin had a certain therapeutic effect on cholestasis. The effect of high dose of SA was similar to that of UDCA group, while SA could up-regulate the expression of FXR, SHP-1, SHP-2, MREP2, BSEP and NTCP, down-regulate the expression of CYP7A1 and CYP27A1, suggesting that the drug plays a role by regulating related proteins. SA has obvious intervention and regulation effect on ANIT-induced intrahe patic cholestasis in young SD rats, with possible therapeutic function by participating in the transport and synthesis of bile acids.