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:20050114:(30400563):(1980),(),,;(1975),(),,,,,Tel.02423986325;(1965),(),,,,,,Tel.02423986321,Emailhezhgui@mail1sy1ln1cn:10062858(2005)06046906Caco2,,(,110016):Caco21974200432,Caco2,Caco2Caco2,,pHCaco2,,:;;Caco2;:R94511:A,,,Caco2(thehumancoloncarcinomacellline),Caco2,Caco2,1Caco2Caco2Fogh1977Caco2:,,20dCaco2,(transepithelialelectricresistance,TEER)Caco2[1]Caco2,pH,Caco2,Caco2:;Caco2,;Caco2,,;Caco2,;;;Caco2,,,2Caco24:226200511JournalofShenyangPharmaceuticalUniversityVol122No16Nov.2005p1469(1)1Thepassivetranscellular;2Thepassiveparacellular;3Theactivecarrier2mediatedtranscellular;4Thetranscytosisroutes;ThearrowsindicatethefourdifferentdrugtransportroutesFig.1Schematicdrawingofanintestinalepithelium211,,1000[2],,,,,[3][4],,,,,[5]P,[6],,,[7],,[8],212Caco2Caco2Caco2[9](Papp110-6)(Papp110-7),Caco2[10],,,Caco2[11],Caco2,,Caco2,,[12],Caco23080[11],2:07422,Caco2,Caco2,,[13],(),,21,IEC18Caco2[14]2Caco2HT29H,2,[15]HT29HCaco250,2,,2,,Caco2Caco2Caco2(),,,L,Caco2100[5],Caco2,L[16],[17],Caco2Caco2,,Caco2,,,Caco2,Caco2[18][19][20],Caco2,,3Caco2311Caco2,:Papp=dQdt1Ac0c0(donor),dQ/dt(receiver),A()PDR=PCaco-2(BA)PCaco-2(AB),PCaco-2(BA)BL(baso2lateral)AP(apical),PCaco-2(AB)APBL()Papp,,PappAB,BA;PCaco-2(BA)PCaco-2(AB),;PCaco-2(BA)/PCaco-2(AB)115,:P(Pglyco2protein,Pgp)(multidrugresistanceprotein,MRP)Caco22,,[2124]1746:Caco2312Caco2,TEER,Papp,,,,Caco2,(Papp),()PappPapp,Caco2,TEERt,[25]313[26],,,Caco2,,(P),,PP,(Papp)P,P,,P[27,28]Caco2,314,[25],1,5(CCKA),(Papp):logPapp=8105-0127n-010065S+0103En,S,E,[29],(),,315,,,,Caco2,,Papp,[30]316Caco2,[20]()Caco2CYPlAlSCaco2[31]P450Caco2,CYP3A,Caco2317pH,,(),Caco2pH,Caco2,[32]274224Caco2,,,,,,Caco2,,,Caco2APBL,:[1],.Caco2[J].,2000,35(10):797-800.[2]PappenheimerJR,ReissKZ.Contributionofsolventdragthroughintercellularjunctionstoabsorptionofnutrientsbythesmallintestineoftherat[J].JMembrBio,1987,100(2):123-136.[3]NellanHN.Paracellularintestinaltransport:modula2tionofabsorption[J].AdvDrugDelivRev,1991,7(3):339-364.[4]FuruseM,HiraseT,ItohM,etal.Occludin:anovelintegralmembraneproteinlocalizingattightjunction[J].JCellBio,1993,123(6Pt2):1777-1788.[5]LennernasH,NilssonD,AquiloniusSM,etal.Theef2fectofL2leucinontheabsorptionoflevodopa,studiedbyregionaljejeunalperfusioninman[J].BrJClinPharmacol,1993,35(3):243-250.[6]Phung2BaV,WarneryA,SchermanD,etal.Interac2tionofpristinamycinIAwithPglycoproteininhumanintestinalepithelialcells[J].EurJPharmacol,1995,288(2):187-192.[7]HunterJ,JepsonMA,TsuruoT,etal.Functionalex2pressionofP2glycoproteininapicalmembranesofhu2manintestinalCaco2cells[J].JBiolChem,1993,268(20):14991-14997.[8]deAizpuruaHJ,RusselJonesGJ.Oralvaccination.I2dentificationofclassesofproteinsthatprovokeanim2muneresponseuponoralfeeding[J].JExpMed,1988,167(2):440-451.[9]ArturssonP,KarlssonJ.Correlationbetweenoraldrugabsorptioninhumansandapparentdrugpermeabilitycoefficientsinhumanintestinalepithelial(Caco2)cells[J].BiochemBiophysResCommun,1991,175(3):880-885.[10]WilsP,WarneryA,Phung2BaV,etal.Differentiatedintestinalepithelialcelllinesasinvitromodelsforpre2dictingtheintestinalabsorptionofdrugs[J].CellBiolToxicol,1994,10(5-6):393-397.[11]LennernasH,PalmK,FagerholmU,etal.Comparisonbetweenactiveandpassivedrugtransportinhumanin2testinalepithelial(Caco2)cellsinvitroandhumanjejunuminvivo[J].IntJPharm,1996,127(1):103-107.[12]WilsonFA,DietschyIM.Theintestinalunstirredwa2terlayer:itssurfaceareaandeffectonactivetransportkinetics[J].BiochimBiophysActa,1974,363(1):112-126.[13]ArturssonP,UngellAL,LofrothJE.Selectivepara2cellualrpermeabilityintwomodelsofintestinalabsorp2tion:culturedmonolayersofhumanintestinalepithelialcellsandratintestinalsegments[J].PharmRes,1993,10(8):1123-1129.[14]MaTY,HollanderD,BhallaD,etal.IEC18,anon2transformedsmallintestinalcelllineforstudyingep2ithelialpermeability[J].JLabClinMed,1992,120(2):329-341.[15]Wikman2LarhedA,ArturssonP.Co2culturesofhumanintestinalgoblet(HT29H)absorption(Caco2)cellsforstudiesofdrugandpeptideabsorption[J].EurJPharmSci,1995,3(3):171-183.[16]HidalgoIJ,BorchardtRT.Transportofalargeneu2tralaminoacid(phenylalanine)inahumanintestinalepithelialcellline:Caco2[J].BiochimBiophysActa,1990,1028(1):25-30.[17]StewartBH,ChanOH,LuRH,etal.Comparisonofintestinalpermeabilitiesdeterminedinmultipleinvit2roandinsitumodels:Relationshiptoabsorptioninhu2mans[J].PharmRes,1995,12(5):693-699.[18]WalterE,KisselT.Heterogeneityinthehumanin2testinalcelllineCaco2leadstodifferencesintransep2ithelialtransport[J].EurJPharmSci,1995,3(4):215-230.[19]NicklinP,IrwinB,HassanI,etal.PermeablesupporttypeinfluencesthetransportofcompoundsacrossCaco2cells[J].IntJPharm,1992,83(1-3):197-209.[20]JumarieC,MaloC.Caco2cellsculturedinserum-freemediumasamodelforthestudyofenterocyticdif2ferentiationinvitro[J].JCellPhysiol,1991,1493746:Caco2(1):24-33.[21],,.9Caco2[J].,2004,39(10):839-843.[22]WalgrenRA,KarnakyKJ,LindenmayerGE,etal.Effluxofdietaryflavoniodquercetin422glucosideacrosshumanintestinalCaco2cellmonolayersbyapi2calmultidrugresistance2associatedprotein22[J].JPharmacolExpTher,2000,294(3):830-836.[23]VaidyanathanJB,Walle
本文标题:Caco_2细胞模型在口服药物吸收研究中的应用
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