| Objective: To investigate the expression of Farnesoid X receptor (FXR) and its target genes including small heterodimer partner(SHP) and Cholesterol-7 -hydroxylase(CYP7A1) in liver of pregnant rats with intrahepatic cholestasis, and to explore the mechanism of intrahepatic cholestasis of pregnancy (ICP) from self-feedback regulation of bile acids synthesis.Methods: 30 SD pregnant rats for 15 days were randomly divided into two groups: estradiol benzoate(EB) group and isotonic Na chloride(NS) group(15 in each), then given respectively the subcutaneously injection of estradiol benzoate at a dose of 2.5 ml·kg-1·d-1and isotonic Na chloride at a dose of 2.5 mg·kg-1·d-1 for 5 days. 2ml blood was taken before and the 5th day after the administration to measure the serum level of ALT, AST, ALP, TBA ,TBIL, DBIL. After delivery, the liver of pregnant rats were taken to observe morphologic changes. Liver was taken for histological analysis with light microscope by HE staining after delivery; some physiological indexs of the fetal rats has been measured. The mRNA and protein expressions of FXR, SHP and CYP7A1 in liver were determined by RT-PCR and Western blotting.Result: The serum level of ALT, AST, ALP, TBA, TBIL, DBIL in EB group increased significiantly(P<0.01), but NS group had no changes (P>0.05); The pathological changes of EB group showed intrahepatic cholestasis; There were no significance (P>0.05) in development of fetal rats between NS and EB groups, but fetal mortality in NS group was lower than in EB group(P<0.01); The mRNA and protein expressions of FXR, SHP and CYP7A1 were significantly higher in EB group than in NS group (P<0.01).Conclusion: Estradiol benzoate is the best candidate for inducing animal model of ICP. Because of cholestasis induced by Estradiol benzoate, the mRNA and protein expressions of FXR, SHP and CYP7A1 in liver were increased, which synthesize more bile acids. This may be one of the mechanisms of ICP. |
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