水通道蛋白4抗体在视神经脊髓炎发病机制中的作用武雷黄德晖吴卫平摘要:视神经脊髓炎(NMO)是主要累及视神经和脊髓的中枢神经系统自身免疫性脱髓鞘疾病,既往在其与多发性硬化的关系上一直存有争议,水通道蛋白4(AQP4)抗体的发现,不但为NMO是独立于MS的疾病实体提供了新的证据支持,而且把NMO的研究推上了一个新的水平。该文就AQP4抗体在NMO发病机制中的作用,包括介导星形胶质细胞损伤、血-脑脊液屏障破坏、炎性反应细胞浸润、少突胶质细胞损伤和髓鞘破坏等方面进行综述。视神经脊髓炎;水通道蛋白4抗体;星形胶质细胞R744.5+2A1006-2963(2011)06-0431-0410.3969/j.issn.1006-2963.2011.06.014100853解放军总医院神经内科万方数据·432·万方数据·433·万方数据@@[1]deSezeJ,LebrunC,StojkovicT,etal.IsDevic'sneuromyelitisopticaaseparatedisease?Acomparativestudywithmultiplesclerosis[J].MultScler,2003,9:521-525.@@[2]GalettaSL,BennettJ.Neuromyelitisopticaisavariantofmultiplesclerosis[J].ArchNeurol,2007,64(6):901-903.@@[3]MisuT,FujiharaK,KakitaA,etal.Lossofaquaporin4inlesionsofneuromyelitisoptica:distinctionfrommultiplesclerosis[J].Brain,2007,130:1224-1234.@@[4]LennonVA,WingerchukDM,KryzerTJ,etal.Aserumautoantibodymarkerofneuromyelitisoptica:distinctionfrommultiplesclerosis[J].Lancet,2004,364:2106-2112.@@[5]LennonVA,KryzerTJ,PittockSJ,etal.lgGmarkerofopticspinalmultiplesclerosisbindstotheaquaporin-4waterchannel[J].JExpMed,2005,202:473-477.@@[6]Amiry-MoghaddamM,FrydenlundDS,OttersenOP.Anchoringofaquaporin-4inbrain:Molecularmechanismsandimplicationsforthephysiologyandpathophysiologyofwatertransport[J].Neuroscience,2004,129:999-1010.@@[7]SainiH,FernandezG,KerrD,etal.Differentialexpressionofaquaporin-4isoformslocalizeswithneuromyelitisopticadiseaseactivity[J].JNeuroimmunol,2010,221..68-72.@@[8]RossiA,PisaniF,NicchiaGP,etal.EvidencesforaleakyscanningmechanismforthesynthesisoftheshorterM23proteinisoformofaquaporin-4:implicationinorthogonalarrayformationandneuromyelitisopticaantibodyinteraction[J].JBiolChem,2010,285:4562-4569.@@[9]NicchiaGP,MastrototaroM,RossiA,etal.Aquaporin-4orthogonalarraysofparticlesarethetargetforneuromyelitisopticaautoantihodies[J].Glia,2009,57:1363-1373.@@[10]LucchinettiCF,MandlerRN,McGavernD,etal.AroleforhumoralmechanismsinthepathogenesisofDevic'sneuromyelitisoptica[J].Brain,2002,125:1450-1461.@@[11]MisuT,FujiharaK,NakamuraM,etal.Lossofaquaporin-4inactiveperivascularlesionsinneuromyelitisoptica:acasereport[J].TohokuJExpMed,2006,209:269-275.@@[12]TakanoR,MisuT,TakahashiT,etal.AstrocyticdamageisfarmoreseverethandemyelinationinNMO:aclinicalCSFbiomarkerstudy[J].Neurology,2010,75:208-216.@@[13]HinsonSR,RoemerSF,LucchinettiCF,etal.Aquaporin-4-bindingautoantibodiesinpatientswithneuromyelitisopticaimpairglutamatetransportbydown-regulatingEAAT2[J].JExpMed,2008,205:2473-2481.@@[14]KinoshitaM,NakatsujiY,MoriyaM,etal.Astrocyticnecrosisisinducedbyanti-aquaporin-4antibody-positiveserum[J].Neuroreport,2009,20.:508-512.@@[15]SabaterL,GiraltA,BoronatA,etal.Cytotoxiceffectofneuromyelitisopticaantibody(NMO-IgG)toastrocytes:aninvitrostudy[J].JNeuroimmunol,2009,215:31-35.@@[16]VincentT,SaikaliP,CayrolR,etal.Functionalconsequencesofneuromyelitisoptica-IgGastrocyteinteractionsonblood-brainbarrierpermeabilityandgranulocyterecruitment[J].JImmunol,2008,181:5730-5737.@@[17]ZhouJ,KongH,HuaX,etal.Alteredblood-brainbarrierintegrityinadultaquaporin-4knockoutmice[J].Neuroreport,2008,19:1-5.@@[18]SaikaliP,CayrolR,VincentT.Anti-aquaporin-4auto-...