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纸质出版:2008
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兰易,刘建,邹姝丽,程浩,甘晓玲.FXR、CYP7A1在妊娠期肝内胆汁淤积症孕鼠胆汁酸代谢中的作用[J].陆军军医大学学报(原第三军医大学学报),2008,30(16):1561-1563.
LAN Yi,LIU Jian,ZOU Shu-li,CHENG Hao,GAN Xiao-ling.Effects of FXR and CYP7A1 on metabolism of acid bile of pregnant rats with intrahepatic cholestasis[J].J Amry Med Univ (J Third Mil Med Univ),2008,30(16):1561-1563.
兰易,刘建,邹姝丽,程浩,甘晓玲.FXR、CYP7A1在妊娠期肝内胆汁淤积症孕鼠胆汁酸代谢中的作用[J].陆军军医大学学报(原第三军医大学学报),2008,30(16):1561-1563. DOI:
LAN Yi,LIU Jian,ZOU Shu-li,CHENG Hao,GAN Xiao-ling.Effects of FXR and CYP7A1 on metabolism of acid bile of pregnant rats with intrahepatic cholestasis[J].J Amry Med Univ (J Third Mil Med Univ),2008,30(16):1561-1563. DOI:
目的 分析法尼醇受体(FXR)及其靶基因胆固醇7α-羟化酶(CYP7A1)在妊娠期肝内胆汁淤积症(intrahepatic cholestasis of pregnancy
ICP)孕鼠肝脏的表达情况,探讨FXR与CYP7A1在ICP发病机制中的作用。 方法 用随机数字表法将30只孕15 d 的SD大鼠分成2组:生理盐水(NS)组和苯甲酸雌二醇(estradiol benzoate
EB)组,每组15只。用药前和用药后第5天分别测定血清中ALT、AST、ALP、TBA水平
同时观察肝脏形态学变化
并应用RT-PCR和Western blot分别检测肝脏FXR、CYP7A1两者mRNA和蛋白的表达。 结果 EB组用药后各血清生化指标比用药前显著升高(P0.01),NS组用药前后无明显变化(P0.05);EB组孕鼠肝脏出现肝内胆汁淤积表现,NS组肝脏形态结构正常;EB组FXR和CYP7A1两者的 mRNA和蛋白表达均显著高于NS组(P0.01)。 结论 EB诱导的ICP孕鼠肝脏FXR及CYP7A1表达均增加,说明存在胆汁酸合成自身反馈调节障碍,导致胆汁酸合成增加
这可能是ICP发病机制之一。
Objective To investigate the expressions of farnesoid X receptor (FXR) and its target gene cholesterol-7α-hydroxylase (CYP7A1) in liver of pregnant rats with intrahepatic cholestasis
and to explore the mechanism of intrahepatic cholestasis of pregnancy (ICP). Methods Thirty SD rats at gestation day 15 were randomly assigned to receive isotonic Na chloride (NS) and estradiol benzoate (EB) for 5 d. Blood (2 ml) was taken before and at the end of 5-day administration to measure the levels of ALT
AST
ALP
TBA
and the liver of pregnant rats after sacrifice were taken to observe morphologic changes. The mRNA and protein expressions of FXR and CYP7A1 in liver were determined by RT-PCR and Western blotting. Results The serum levels of ALT
AST
ALP
TBA in EB rats increased significantly (P0.01)
and the pathological changes of EB rats proved intrahepatic cholestasis. The mRNA and protein expressions of FXR and CYP7A1 were significantly higher in EB rats than NS rats (P0.01). Conclusion Estradiol benzoate is the best candidate for inducing rat model of ICP. The mRNA and protein expressions of FXR and CYP7A1 in liver were increased
resulting in increased synthesis of bile acids
which may be one of the mechanisms of ICP.
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