Abstract:

Objective To study the expression of estrogen receptor(ER) and gene related to regulation of bile acid metabolism in fetal rat liver of pregnant rats with intrahepatic cholestasis.
Methods Sixty clean SD pregnant rats were selected and divided into two groups at random. ① Since the 13th day of pregnancy after taking blood, the rats in control group were injected subcutaneously with refined vegetable oil 2.5 mL·kg^-1·d^-1, study group was injected subcutaneously with the 17-α-ethynylestradiol(EE) 1.25 mg·kg^-1·d^-1 till the 17th day. ② On the 21st day, all rats were killed. Then the fetus livers were collected for study. ③ The levels of serum total bile acid(TBA) were examined by ELISA. The expression of ER, CYP7A1, CYP27A1, CYP8B1(mRNA) in fetal rat liver was examined by real-time PCR.
Results ① The levels of TBA were significantly higher in study group mother rats(58.7±3.2)μmol/L than that of control group(24.6±1.3)μmol/L on the 17th day(P<0.05); The levels of TBA were higher in study group mother rats(66.4±2.7)μmol/L than that of control group(26.5±3.1)μmol/L on the 21st day(P<0.05）. The levels of TBA were higher in study group fetus rats（28.4±2.6）μmol/L than that of control group（10.5±3.1）μmol/L on the 21st day. ② The expression of CYP7A1 mRNA（1.25±0.01）, CYP27A1 mRNA（2.05±0.03）, CYP8B1 mRNA（1.85±0.01） in study group fetus liver increased as compared to control group（0.35±0.02, 0.75±0.03, 0.85±0.02, respectively）（P<0.05）. 3) The expression of ERα mRNA in study group（0.75±0.02）was higher than that of control group（0.45±0.01）（P<0.05）. Conclusion The expression of ERα, CYP7A1, CYP27A1, CYP8B1(mRNA ) increased in the fetal rat liver of pregnant rats with intrahepatic cholestasis, resulting in increased synthesis of bile acids, which may be one of the mechanisms of perinatal death of the fetal rats.

Key words: cholestasis, liver, pregnant rat, estrogen receptor, cholesterol 7&alpha, -hydroxylase, cholesterol 12&alpha, -hydroxylase