Effect of emodin on transporter gene expression of hepatocytes in intrahepatic cholestatic rats
AIM: To investigate the effect and mechanism of emodin on acute intrahepatic choles-tasis in rats. METHODS: Acute cholestatic model in rats was induced by alpha-naphthyliso thiocya-nate( ANIT). Normal control group, emodin group without ANIT treatment, model group and emodin group with ANIT treat ment were set up. liver function and pathological changes of hepatic tissue were examined. Real-time fluorescent quantitative RT-PCR was used to detect the mRNA levels of the hepatic transporter bile salt export pump( BSEP) ,multidrug resistance-asso ciated protein 2 ( MRP2 ) , Na ~+ /taurocholate cotransporting peptide (NTCP) , multidrug resistance protein 2( MDR2), multidrug resist ance-associated protein 3 ( MRP3 ) and the nuclear receptor farne soid X receptor (FXR). RESULTS: In the model group compared with the normal control group, the concentrations of serum total bil irubin ( TB ) , direct bilirubin ( DB ) , alanine aminotransferase ( ALT ) , aspartate aminotransferase ( AST ) , alkaline phosphatase (ALP) and total bile acid ( TBA ) were increased ( P < 0. 01 ) ; inflammatory cell infiltration, hepatic cellular change and necrosis could be observed by light microscop; the genes expression of NT CP and FXR were down-regulated ( P < 0. 01 ), the MDR2 and MRP3 were up-regulated ( P < 0. 01 or P < 0. 05 ). But the expression of BSEP and MRP2 could not be affected. However,by emod in treatment, the concentrations of TB, DB, ALT, AST, ALP and TBA were decreased ( P < 0. 01 or P < 0. 05 ) ; Only mild his topathological change in liver could be seen;the genes expression of NTCP,MDR2 and MRP3 were higher than those of the model group(P<0. 05) ,but the expression of BSEP, FXR and MRP2 could not be affected. In emodin group without ANIT treatmentcompared with the normal control group,the changes of liver function, histopathology and transporter genes were not significantly different. CONCLUSION: Emodin has a protective effect on hepatocytes and a restoring activity on cholestatic hepatitis. Mechanism of its action may be related to induce expression of the bile metabolism-related transporter NTCP,MDR2 and MRP3 in the liver to prevent bile acids overaccumulation in hepatocytes and hepatic toxicity.
NETL
NSTL
万方数据
维普
