星形胶质细胞的研究_张敬军

星形胶质细胞的研究(泰山医学院附属医院神经内科,山东泰安　271000):2006-02-03,:2006-03-18:(NoY2000C23);:(1963-),,,,:、,Tel:[phone],E-mail:[e-mail]:R-05;R322.81;R329.2;R329.24;R341;R74:A:1001-1978(2006)07-0788-04:,、、、,。:;;　　,。,Na+、K+Ca2+,、、[1],,、、、、、,(CNS),[2～6]。,,,,“”。,。1　　　,,。(astrocyte,AS),。AS:①AS:,,,。(glialfibrillaryacidicprotein,GFAP)。②AS:,,,。AS,。。,、[7]。AS、,AS、、、、6,AS。,,[8]。2　2.1　GFAP　CNS,。GFAP。,,GFAP,,GFAP[3]。,,。ASCNS。ASCNS。2.2　GFAP　GFAPcDNAGFAP。BrennerGFAP。、GFAP,GFAP90%～95%,3′。GFAP17,22,GFAP。GFAP-250bp～-80bp-1980bp～-1500bp,-650bp～-360bp。GFAP-(cAMP)、NF-1、Sp-1、Ap-1Ap-2。,、。GFAP,·788·中国药理学通报　ChinesePharmacologicalBulletin　2006Jul;22(7):788～91GFAP,GFAP,、[4]。2.3　GFAP　GFAPmRNA3.4kb,GFAP-α,GFAP-βGFAP-γ。GFAPmRNA。、,。GFAP,。GFAP,。GFAP,。GFAP,4。GFAPcdc2、CcAMP。GFAP,GFAP。GFAP,。3　3.1　　ASCNS,。AS。、、。3.2　　CNS,AS,GABAASAS,AS,,,GABA。AS,。AS(、5-)。3.3　[1]　AS,pH,K+,。AS,AS。ASK+Ca2+、IP3、cAMP。ASK+K+,,K+。AS,Mg2+Ca2+,。3.4　　AS20,,,(NGF)、(bFGF)、、[5],、、[9～11]。9dAS,10d,AS,。ASbFGFGABAc-fos。AS。AS,ASThy-1()。。3.5　　(GFP),。,8,,;,[12]。。,,[13]。3.6　　,,。,。,,。,。,[14]。[15]。,·789·中国药理学通报　ChinesePharmacologicalBulletin　2006Jul;22(7)。3.7　　,。ASE、(SOD),,[16],AStbOOHPC12,,AS,H2O2。3.8　　AS(BBB),BBBCNS,CNS,。,AS。ASCNS[17],AS,。ASMHCIIB7,CD4+、CD8+T,T。T,AST。AS,[18]。AS,BBB,[19]。4　4.1　　AS、,、、,,,。,AS,iNOS,NO,DNA,[20]。[21]。AS。GFAP,GFAP[22]。4.2　　。、,,4-,,,[23]。,AS[24],AS,K+,K+,。,GABA,GABA,,。4.3　(Parkinsonsdisease,PD)　,,。,AS,,PD。ASPD,。,B(MAOB)“”,MAOB1--4-(MPP+),MPP+,PD。PD,,ASNGF。4.4　(Alzheimersdisease,AD)　AD,,AD。(senileplaques,SP),,SP,SP,AS,ASSP。ASSP,,Aβ。NO,NO。,,NMDA,Ca2+,NO。IFN-γIL-1iNOSNO,NO,ONOO-,,,,,。ASAβPC12,Aβ。[25],,[26]。4.5　　Hungtington、、CNS[27]、AS、,。,ASCNS,,。,AS·790·中国药理学通报　ChinesePharmacologicalBulletin　2006Jul;22(7),AS,CNS,AS、,。:[1]　SharmaG,VijayaraghavanS.Nicotiniccholinergicsignalinginhippocampalastrocytesinvolvescalcium-inducedcalciumreleasefromintracellularstores[J].ProcNatlAcadSciUSA,2001,98(7):4148-53.[2]　VoutsinosPB,BonventoG,TanakaK,etal.Glialglutamatetransportersmediateafunctionalmetaboliccrosstalkbetweenneu-ronsandastrocytesinthemousedevelopingcortex[J].Neuron,2003,37(2):275-86.[3]　GomesFC,PaulinD,MouraNV,etal.Glialfibrillaryacidicprotein(GFAP):modulationbygrowthfactorsanditsimplicationinastrocytedifferentiation[J].BrazJMedBiolRes,1999,32:619-31.[4]　TrejoF,VergaraP,BrennerM,etal.Genetherapyinarodentmodelofparkinson′sdiseaseusingdifferentiatedC6cellsexpress-ingaGFAP-tyrosinehydroxylasetransgene[J].LifeSci,1999,65:483-91.[5]　AlbrechtPJ,DahlJP,StoltzfusOK,etal.Giliaryneurotrophicfactoractivatesspinalcordastrocytes,stimulatingtheirproductionandreleaseoffibroblastgrowthfactor-2,toincreasemotorneuronsurvival[J].ExpNeurol,2002,173(1):46-62.[6]　EmsleyJG,ArlottaP,MacklisJD.Star-cross'dneurons:astrogen-lialeffectsonneuralrepairintheadultmammalianCNS[J].TrendsNeurosci,2004,27(5):238-40.[7]　KimelbergHK.Theproblemofastrocyteidentity[J].NeurochemInt,2004,45(2-3):191-202.[8]　TagaT,FukudaS.RoleofIL-6intheneuralstemcelldifferentia-tion[J].ClinRevAllergyImmunol,2005,28(3):249-56.[9]　PavelkoKD,HoweCL,DrescherKM,etal.Interleukin-6pro-tectsanteriorhornneuronsfromlethalvirus-inducedinjury[J].JNeurosci,2003,23(2):481-92.[10]GabrielC,AliC,LesneS,etal.Transforminggrowthfactoralpha-inducedexpressionoftype1plasminogenactivatorinhibitorinas-trocytesrescuesneuronsfromexcitotoxicity[J].FASEBJ,2003,17(2):277-9.[11]MinKJ,YangMS,JouI,etal.ProteinkinaseAmediatesmicro-glialactivationinducedbyplasminogenandgangliosides[J].ExpMolMed,2004,36(5):461-7.[12]SongH,StevensCF,GageFH.Astrogliainduceneurogenesisfromadultneuralstemcells[J].Nature,2002,417:39-44.[13]SvendsenCN.Theamazingastrocyte[J].Nature,2002,417:29-31.[14]BeattieEC,StellwagenD,MorishitaW,etal.ControlofsynapticstrengthbyglialTNFα[J].Science,2002,295:2282-5.[15]MauchDH,NaglerK,PriegerFW,etal.CNSsynaptogenesispro-motedbyglia-derivedcholesterol[J].Science,2001,294:1354-7.[16]WangXF,CynaderMS.Astrocytesprovidecysteinetoneuronsbyreleasingglutathione[J].JNeurochem,2000,74:1434-42.[17]WheelerRD,CollinsPD,etal.IdentificationofatruncatedIL-18RbetamRNA:aputativeregulatorofIL-18expressedinratbrain[J].JNeuroimmunol,2003,145(1):40-5.[18]DongY,BenvenisteEN.Immunefunctionofastrocytes[J].Glia,2001,36:180-90.[19]PratA,BiernackiK,WosikK,etal.Gliacellinfluenceonthehu-manbloodbrainbarrier[J].Glia,2001,36(2):145-55.[20],　,　,.[J].中国药理学通报,2005,21(5):584-7.[21]GiffardRG,SwansonRA.Ischemia-inducedprogrammedcelldeathinastrocytes[J].Glia,2005,50(4):299-306.[22]NawashiroH,BrennerM,FukuiS,etal.Highsusceptibilitytocer-ebralischemiainGFAP-nullmice[J].JCerebBloodFlowMetab,2000,20:1040-4.[23]RossFM,GwynP,SpanswickD,etal.CarbenoxolonedepressesspontaneousepileptiformactivityintheCA1regionofrathipp-ocampalslices[J].Neuroscience,2000,100(4):789-96.[24]PetroffOA,ErranteLD,KimJH,etal.N-acetyl-aspartate,totalcreatine,andmyo-inositolintheepileptogenichumanhippocam-pus[J].Neurologe,2003,60(10):1646-51.[25]NicholsNR,AgolleyD,ZiebaM,ByeN.Glucocorticoidregulationofglialresponsesduringhippocampalneurodegenerationandre-generation[J].BrainResBrainResRev,2005,48(2):287-301.[26]EndoT.Glyca