[Effects of farnesoid X receptor ligand on the metabolism of bile acids in rats with estrogen-induced intrahepatic cholestasis of pregnancy].
OBJECTIVE
To investigate the effects and mechanism of farnesoid X receptor (FXR) and its ligands on the metabolism of bile acids in rats with estrogen-induced intrahepatic cholestasis of pregnancy (ICP).


METHODS
An ICP rat model was established with estradiol benzoate (EB) injections. Then FXR ligand chenodeoxycholic acid (CDCA) was administrated (100 mg/kg daily) to ICP rats for 5 days. The serum TBA and expression of FXR and bile salt export pump (BSEP) in the rat livers were examined by immunohistochemistry and reverse transcription PCR.


RESULTS
The levels of TBA in the CDCA group rats were significantly lower than the untreated rats [(17.2+/-4.1)micromol/L vs (29.3+/-6.4)micromol/L], and the expressions of mRNA and protein of FXR were significantly higher [(0.76+/-0.09 vs 0.53+/-0.06, P<0.05 and 2.35+/-0.06 vs 1.83+/-0.05, P<0.017, respectively)], and the expressions of BSEP were also higher [(0.99+/-0.21 vs 0.76+/-0.07, P<0.017 and 1.88+/-0.03 vs 1.46+/-0.06, P<0.017, respectively)].


CONCLUSIONS
FXR plays an important role in modulating the metabolism of bile acids. CDCA can lower the levels of serum TBA by upregulating the expression of FXR and BSEP and then increasing the transport of the bile acids. These facts might present a new idea and target for the treatment of ICP.
Zou
Shu-li
SL
Department of Obstetrics and Gynecology, Second Affiliated Hospital of Chongqing University of Medical Sciences, Chongqing 400010, China.
Liu
Jian
J
Lan
Yi
Y
Cheng
Hao
H
Gan
Xiao-lin
XL
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D002635:Chenodeoxycholic Acid / Q000494:pharmacology*; D002780:Cholestasis, Intrahepatic / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D011247:Pregnancy; D011248:Pregnancy Complications / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D000099150:Receptor, Farnesoid X-Activated
D001647:Bile Acids and Salts; D002635:Chenodeoxycholic Acid; D004967:Estrogens; D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated