收藏本站
收藏 | 手机打开
二维码
手机客户端打开本文

Activation of the constitutive androstane receptor promotes bilirubin clearance in a murine model of alcoholic liver disease

Xiuyan Wang  Liyu Zheng  Jinming Wu  Xianfan Lin  Wenzhi Wu  Rong Jin  Zhiming Huang  Jiansheng Wu  
【摘要】:Background:Increased bilirubin level in the plasma has been reported in alcoholic liver disease(ALD)rat and different stage of ALD patients.The constitutive androstane receptor(CAR)is known as a xenobiotics receptor that induces the detoxification and transport of bilirubin.In our study,we are aimed to investigate systematic bilirubin transport regulatory mechanisms and the role of activation of CAR on hepatic and extrahepatic bilirubin clearance pathway in a murine model of ALD.Methods:Mice were fed Lieber-DeCarli ethanol diet or an isocaloric control diet for 4 weeks followed by administration of CAR agonists TCPOBOP and phenobarbital and their vehicles to study the effect of pharmacological activation of CAR on serum bilirubin level and bilirubin clearance pathway in ALD.Results:Chronic ethanol ingestion resulted in elevated serum bilirubin level,suppression of hepatic and renal OATPlal and hepatic MRP2 expression,and induction of UGTl Al expression accompanied by impairment of CAR's translocation to the nuclear.However,activation of CAR by different ligands TCPOBOP and phenobarbital downregulated serum bilirubin level and selectively upregulated OATPlal,0ATPla4,UGT1A1 and MRP2expression in a murine model of ALD.Conclusions:Our results reveal bilirubin transport regulatory mechanisms in a murine model of ALD,highlight the key role of CAR in the modulation of bilirubin clearance pathway and suggest a possible therapeutic value for CAR ligands in ALD treatment.

知网文化
【相似文献】
中国期刊全文数据库 前4条
1 贲晓明 ,秦玉明 ,吴圣楣 ,张惠民 ,陈舜年 ,夏振炜;EXPERIMENTAL AND CLINICAL STUDY ON BILIRUBIN NEUROTOXICITY DETECTED BY VISUAL EVOKED POTENTIALS TO FLASH[J];Journal of Shanghai Second Medical University;2001年01期
2 ;A rat model for acute hepatic failure[J];Hepatobiliary & Pancreatic Diseases International;2003年03期
3 ;Affinity Adsorption of Bilirubin on Cibacron Blue F3GA-modified Microporous Polytetrafluoroethylene Capillary[J];Chemical Research in Chinese Universities;2010年02期
4 ;[J];;年期
 快捷付款方式  订购知网充值卡  订购热线  帮助中心
  • 400-819-9993
  • 010-62982499
  • 010-62783978