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1、FXR、CYP7A1在妊娠期肝内胆汁淤积症孕鼠胆汁酸代谢中的作用作者：兰易,刘建,邹姝丽,程浩,甘晓玲单位：重庆医科大学附属第二医院妇产科,重庆 摘 要: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(intrahe-paticcholestasisofpregnancy,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15d的SD大鼠分成2组:生理盐水(NS)组和苯甲酸雌二醇(estradiolbenzoate,EB)组,每组15只。用药前和用药后第5天分别测
2、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Westernblot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(P<0•01),NS组用药前后无明显变化(P>0•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(P<0•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
3、能是ICP发病机制之一。 关键词:孕鼠;胆汁淤积,肝内;法尼醇受体;胆固醇7α-羟化酶 中图法分类号:R333.3;R34;R714.25文献标识码:AEffectsofFXRandCYP7A1onmetabolismofacidbileofpregnantratswithintra-hepaticcholestasisLANYi,LIUJian,ZOUShu-li,CHENGHao,GANXiao-ling(DepartmentofObstetricsandGynecology,TheSecondAffiliatedHospital,ChongqingMedical
4、university,Chongqing400010,China) Abstract:Objective ToinvestigatetheexpressionsoffarnesoidXreceptor(FXR)anditstargetgenecholesterol-7α-hydroxylase(CYP7A1)inliverofpregnantratswithintrahepaticcholestasis,andtoexplorethemechanismofintrahepaticcholestasisofpregnancy(ICP).Methods ThirtySDra
5、tsatgestationday15wererandomlyassignedtoreceiveisotonicNachloride(NS)andestradiolbenzoate(EB)for5d.Blood(2ml)wastakenbeforeandattheendof5-dayadministrationtomeasurethelevelsofALT,AST,ALP,TBA,andtheliverofpregnantratsaftersacrificeweretakentoobservemorphologicchanges.ThemRNAandproteinex-pression
6、sofFXRandCYP7A1inliverweredeterminedbyRT-PCRandWesternblotting.Results TheserumlevelsofALT,AST,ALP,TBAinEBratsincreasedsignificantly(P<0•01),andthepathologicalchangesofEBratsprovedintrahepaticcholestasis.ThemRNAandproteinexpressionsofFXRandCYP7A1weresignifi-cantlyhigherinEBratsthanNSrat
7、s(P<0•01).Conclusion Estradiolbenzoateisthebestcandidateforin-ducingratmodelofICP.ThemRNAandproteinexpressionsofFXRandCYP7A1inliverwereincreased,resultinginincreasedsynthesisofbileacids,whichmaybeoneofthemechanismsofICP.
