法尼醇X受体激动剂对雌激素诱导的肝内胆汁淤积症孕鼠胆汁酸代谢的影响及其分子机制  

Effects of farnesoid X receptor ligand on the metabolism of bile acids in rats with estrogen-induced intrahepatic cholestasis of pregnancy

作　　者：邹姝丽[1] 刘建[1] 兰易[1] 程浩[1] 甘晓玲[1] 

机构地区：[1]重庆医科大学附属第二医院妇产科,400010

出　　处：《中华肝脏病杂志》2008年第5期383-386,共4页Chinese Journal of Hepatology

基　　金：重庆市医学科研基金（03-2-049）

摘　　要：目的研究法尼醇X受体（FXR）激动剂鹅去氧胆酸（CDCA）对雌激素诱导的肝内胆汁淤积孕鼠胆汁酸代谢的影响及其分子机制。方法用苯甲酸雌二醇诱导孕鼠发生肝内胆汁淤积，建立妊娠期肝内胆汁淤积症（ICP）模型，将FXR激动剂CDCA作用于ICP模型组，比色法检测孕鼠血总胆汁酸，RT—PCR和免疫组织化学法检测孕鼠肝组织FXR及其靶基因胆盐转运泵（BSEP）的mRNA及蛋白质表达。结果与模型组相比，CDCA治疗组孕鼠血清胆汁酸水平明显降低[（17．2±4．1）μmol／L比（29．3±6．4）μmol／L，P〈0．017]，肝组织FXRmRNA（0．76±0．09比0．53±0．06，P〈0．05）及蛋白质表达（2．35±0．06比1．83±0．05，P〈0.017）明显升高，BSEPmRNA（0．99±0．21比0．76±0．07，P＜0．017）及蛋白质表达（1．88±0．03比1．46±0．06，P〈0．017）也明显升高。结论FXR在调节胆汁酸代谢过程中起重要作用，其激动剂CDCA通过上调BSEP的表达促进胆汁酸转运降低血胆汁酸水平，可能为ICP的治疗提供新的思路和药物靶点。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 irnmunohistochemistry 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）/a mol/L vs （29.3 ± 6.4）/a mol/L, P 〈 0.017], 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.

关 键 词：妊娠并发症 胆汁淤积 肝内 胆汁酸 法尼醇X受体 

分 类 号：R714.2[医药卫生—妇产科学]