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Effect Of Ursodeoxycholic Acid On The Expression Of The Hepatocellular BSEP And FXR In Pregnant Rats With Ethinylestradiol Induced Intrahepatic Cholestasis

Posted on:2006-04-04Degree:MasterType:Thesis
Country:ChinaCandidate:H LiuFull Text:PDF
GTID:2144360155451241Subject:Gynecology
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Objective: To examination the effects of Ursodeoxycholic acid (UDCA) on the expression of hepatocellular Bsep and Fxr in pregnant rats with Ethinylestradiol induced intrahepatic cholestasis. Methods: Fourty trimester pregnant rats were randomized divided into four groups: EE group, PG group ,UDCA group, UDCA+EE group.In the EE group, rats were subcutaneously injection of the appropriate volume of Propylene Glycol(PG) for 5 days; In the UDCA group, rats were received only UDCA at a dose of 50mg.kg-1.d-1 for 5days; in the UDCA+EE group, rats were administered the same dose of EE and per os UDCA at a dose of 50mg.kg-1.d-1 for 5 days, Tow ml blood was taken before and 5 days after the treatment to measure the level of AST,ALT, ALP, TBA. After delivery, the liver of pregnant rats were taken to observe morphologic changes and the growth and development of the fetal rats was also observed. The expression of Bsep and Fxr in liver was analyzed by immunohistochemical method (SP). Results: The serum levels of ALT, AST, ALP, TBA in the EE group rats increased significiantly(p<0.05).PG groups had no changes (p>0.05). UDCA and UDCA+EE group the level of ALT, AST, ALP had on changes (p>0.05) but TBA increased significantly(p<0.05). The pathological changes showed intrahepatic cholestasis in pregnant rats in EE group. Body weight and length, and tail length of fetal rats in the EE group was lighter and shorter than those of other three groups (p<0.05). The expression of hepatocellular Bsep were lower (p<0.05) but the Fxr were higher (p<0.05) in the rats treatment with EE than in the other three groups. Conclusion: UDCA can protect the liver from the injure of intrahepatic cholestasis and improve the outcoming of fetal rats. This improvement is related to a normalization of the expreesion of the bile acid canalicular transporter Bsep and it has on influence on the expression of Fxr.
Keywords/Search Tags:Ursodeoxycholic Acid, Ethinylestradiol, Rat, Cholestasis, intrahepatic, bile salt export pump(Bsep), Farnesoid X receptor(Fxr)
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