_FXR和LXR核受体在胆汁酸-胆固醇代谢中的作用

··FXＲLXＲ－TheroleofnuclearreceptorsFXＲandLXＲinbileacid-cholesterolmetabolism曹艳纯，李风华，张幸CAOYan-chun，LIFeng-hua，ZHANGXing201203－。－。XfarnesoidXreceptorFXＲX1iverXreceptorLXＲ－。胆汁酸－胆固醇代谢;法尼酯衍生物X受体;肝X受体Ｒ333.6A1004－1257201403－0420－04TheroleofnuclearreceptorsFXＲandLXＲinbileacid-cholesterolmetabolismCAOYan-chunLIFeng-huaZHANGXingExperimentCenterforScienceandTechnologyShanghaiUniversityofTraditionalChineseMedicineShanghai201203ChinaAbstractThebileacidisanimportantpartofthebileanditssynthesisisthemainapproachofthecholesteroldegradationwhichplaysavitalroleintheregulationofbileacid-cholesterolmetabolism．Inrecentyearstherehasbeenanewunderstandingfornu-clearreceptorsinthebileacid-cholesterolmetabolism．ThepaperbrieflyreviewssomenewprogressoffarnesoidXreceptorFXＲandliverXreceptorLXＲinbileacid-cholesterolmetabolism．KeywordsBileacid-cholesterolmetabolismFarnesoidXreceptorFXＲLiverXreceptor12ZＲ14317002010JW252012J007A/FXＲ。[e-mail]。－XFXＲ、XLXＲ、XpregnaneXreceptorPXＲ、DvitaminDreceptorVDＲαperoxisomeproliferator-activatedreceptoralphaPPAＲɑ—。——。FXＲLXＲ—。2。1FXＲ－。classicalpathwayalternativepathway2。。。。。bilesaltexportpumpBSEP1。。2。3FXＲFXＲ。FXＲ4。FXＲ5。chenodeoxycholicacidCDCAFXＲ6。FXＲ7ɑ-cholesterol7ɑ-hydroxylaseCYP7A1、smallheterodimerpartnerSHP、BSEP、apicalsodium-dependentbileacidtransporterASBT、ileumbileacidbindingproteinIBABP·024·20142303OccupandHealthFeb.2014Vol.30No.3terminalapi-calsodium-dependentbileacidtransportertASBT、sodiumtaurocholatecontransportpeptideNTCP、phospholipidtransferproteinPLTPlipoproteinlipaseLPL、C-llapolipoprteinC-llapoC-ll、C-lllapolipoprteinC-lllapoC-lll、AbileacidCoAsynthetaseBacs、AN-bileacidCoAaminoacidN-acetyltransferaseBat、3multidrugresist-ance3MDＲ3。FXＲXＲXＲ7。FXＲCYP7A18。FXＲFXＲSHPCYP7A19-11。FXＲCYP7A1。FXＲBSEP12。IBABPFXＲFXＲIBABP。IBABPIBABPFXＲ13。IBABP。FXＲBSEP14SHPNTCP15。FXＲLPLapoC-llapoC-lllverylowdensitylipoproteinreceptorVLDLＲtriglycerideTG16。FXＲBacsBat17。FXＲBacsBat18。FXＲMDＲ3。MDＲ3、、19。FXＲ。2LXＲLXＲLXＲaLXＲb。LXＲ2DNA77%20。LXＲ21。LXＲa－、LXＲβ22。LXＲLXＲ、、23。LXＲa。LXＲɑ24。LXＲXretinoidXreceptorＲXＲ25。LXＲoxystrolLXＲ26。LXＲ。LXＲCYP7A1、EapolipoproteinapoE、ATP-bindingcassettetransporterABC、AlATP-bindingcassettetransporterAIABCAl、G1ATPbindingcassettetransporterG1ABCG1、cholesterolestertransferproteinCETP、LPL、PLTP。LXＲCYP7A1。LXＲaCYP7al27。CYP7A1CYP7A1。LXＲɑ－LXＲɑＲXＲLXＲ28。apoE。LXＲapoE29。LXＲABCA1Gl。ABCAlABCGl。ABCLXＲ30。LXＲLPL。LPLhighdensitylipoproteinHDL31。CETPLXＲLXＲ。CETPHDLTG32。LXＲHDL。LXＲABC、CETP、apoELPLLXＲ33。LXＲ。·124·20142303OccupandHealthFeb.2014Vol.30No.33－。。。。34。－。、35。－。。36。37。。。。。38。DNA。39。4、。。FXＲLXＲ2－－。－、。1ChiangJYL．Bileacidregulationofgeneexpressionroleofnuclearhor-monereceptersJ．EndocrＲev200223443－463．2LefebvrePCariouBLienFetal．Ｒoleofbileacidsandbileacidre-ceptorsinmetabolicregulationJ．PhysiolＲev200989147－191．3DavidWＲussellL．FiftyyearsofadvancesinbileacidsynthesisandmetabolismJ．LipidＲesASBMB200950120－125．4ＲisteaPIHellebnidCAAnthonvLetal．ThenuclearreceptorFXＲisexpressedinpancreaticβ-cellsandprotectshumanisletsfromlipotoxici-tyJ．FEBSLett20105842845－2851．5KrzysztofW.ＲomaSKI．Theroleandmechanismofactionofbileacidswithinthedigestivesystem-bileacidsintheliverandbileJ．AdvClinExpMed200716793－799．6TeodoroJSＲoloAPPalmeiraCM．HepaticFXＲkeyregulatorofwhole-bodyenergymetabolismJ．TEM201122458-466．7ZhuYLiFGuoGL．Tissue-specificfunctionoffarnesoidXreceptorinliverandintestineJ．PharmacolＲes201163259-265．8SongKHChiangJY．GlucagonandcAMPinhibitcholesterol7alpha-hydroxylaseCYP7A1geneexpressioninhumanhepatocytesdiscordantregulationofbileacidsynthesisandgluconeogenesisJ．Hepatology200643117－125．9FangSMiaoJXiangLetal．Coordinatedrecruitmentofhistonemeth-yltransferaseG9aandotherchromatin-modifyingenzymesinSHP-media-tedregulationofhepaticbileacidmetabolismJ．MolCellBiol2007271407－1424．10LeeYSKimDKKimYDeta1．OrphannuclearreceptorSHPinter-actswithandrepresseshepatocytenuclearfactor-6HNF-6transacti-vationJ．Biochemistry2008413559-569．11ChandaDParkJHChoiHS．MolecularbasisofendocrineregulationbyorphannuclearreceptorsmallheterodimerpartnerJ．EndocrJ200855253-268．12MorganＲETraunerMvanStadenCJeta1．InterferencewithbilesaltexportpumpfunctionisasusceptibilityfactorforhumanliverinjuryindrugdevelopmentJ．ToxicolSci2010118485-500．13TokeOMonseyJDDeKosterGTetal．DeterminantsofcooperativityandsiteselectivityinhumanilealbileacidbindingproteinJ．Bio-chemistry200645727－737．14FattingerKFunkCPantzeMetal．Theendothelinantagonistbosen-taninhibitsthecanalicularbilesaltexportpumpapotentialmecha-nismforhepaticadversereactionsJ．ClinPharmacolTher200169223-231．15TrottKＲDoerrWFacoettiAetal．BiologicalmechanismsofnormaltissuedamageImportanceforthedesignofNTCPmodelsJ．Ｒadioth-erOncol201210579－85．16KaderiMAKanduriMBuhlAMetal．LPListhestrongestprognos-ticfactorinacomparativeanalysisofＲNA-basedmarkersinearlychro-niclymphocyticleukemiaJ．Haematologica2011961153－1160．17KwakyeJBBarnesSDiastoＲB．IdentificationofbileacidcoenzyrneAsynthetaseinratdidneyJ．JLＲ19933495－99．18CostetPLuoYWangNetal．Sterol-dependenttransactivationoftheABC1promoterbytheliverXreceptor/retinoidXreceptorJ．BiolChem200027528240－28245．19PatelPWeeraseker