title: [Expression of FXR mRNA, PPAR alpha mRNA and bile acid metabolism related genes in intrahepatic cholestasis of pregnant rats].
abstract: OBJECTIVE
  To study the expressions of FXR, PPARa and Bile acid metabolism related genes in intrahepatic cholestasis of pregnant rats.
  
  
  METHODS
  60 clean SD pregnant rats were selected and divided randomly into three groups. Since the 13th day of pregnancy rats in control group were injected subcutaneously with refined vegetable oil 2.0 mg/kg/d Rats in no-treated group were injected subcutaneously with the 17-a-ethynylestradiol (EE) 1.25 mg/kg/d until the 17th day. Those rat ih treated group were injected subcutaneously with the 17-a-ethynylestradiol (EE) 1.25 mg/kg/d until the 17th day and then were treated with fenofibrate for another four days until the 21th day. All rats were killed at the 21th day and livers were collected for study. The levels of serum TBA were examined by ELISA. The mRNA expressions of PPARa, FXR, CYP7A1, CYP27A1 and CYP8B1 were examined by real-time PCR. (1)
  
  
  RESULTS
  The levels of TBA were significantly higher in no-treated group (68.7+/-4.2)mumol/L and treated group (69.5+/-3.8)mumol/L compared with that of control group (26.6+/-2.3)mumol/L at the 17th day (P value is less than 0.05) and no difference found between treated and no-treated groups (P value is more than 0.05). The levels of TBA were higher in no-treated group (69.4+/-3.7)mumol/L and treated group (48.5+/-4.8)mumol/L as compared to control group (27.1+/-3.2)mumol/L at the 21th day (P value is less than 0.05). The lever of TBA was significantly lower in Treated group compared with No-treated group (P value is less than 0.05). (2) The mRNA expressions of CYP7A1, FXR, CYP27A1 and CYP8B1 increased in No-treated group (1.55+/-0.03, 1.75+/-0.02, 2.45+/-0.01, 2.15+/-0.01, respectively) and were all higher as compared to control group (0.75+/-0.02, 1.25+/-0.03, 0.65+/-0.03, 1.50+/-0.02, respectively) (P value is less than 0.05). However, the mRNA expression of PPARa decreased in No-treated group (0.85+/-0.02) compared with control group (1.45+/-0.02) (P value is less than 0.05). The mRNA expressions of CYP27A1, PPARa and CYP8B1 increased in treated group (1.25+/-0.01, 1.65+/-0.05, 1.65+/-0.02, respectively) and were all higher than that of control group (P value is less than 0.05).
  
  
  CONCLUSIONS
  Abnormal expressions of CYP7A1, FXR, CYP27A1, CYP8B1 and PPARa may play a role in pathogenesis of estrogen-induced intrahepatic cholestasis. Activator of PPARa may be used as therapeutical drug for ICP.
authors.affiliation: Department of Obstetrics and Gynecology, Beijing Shijitan Hospital, Beijing 100038, China. shiqingyun1@163.com
authors.forename: Qing-yun
authors.initials: QY
authors.lastname: Shi
authors.forename: Yu-geng
authors.initials: YG
authors.lastname: Lin
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.forename: Ying-qi
authors.initials: YQ
authors.lastname: Lin
authors.forename: Shi
authors.initials: S
authors.lastname: Yan
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D002780:Cholestasis, Intrahepatic / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism; D004997:Ethinyl Estradiol / Q000008:administration & dosage; D005260:Female; D047493:PPAR alpha / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D001647:Bile Acids and Salts; D002790:Cholesterol 7-alpha-Hydroxylase; D004997:Ethinyl Estradiol; D047493:PPAR alpha; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated