代谢组学及其研究方法和应用

[](,210002),[1]801985,Nicholson(NMR),[2],1999,(metabonom2ics),,,,,,,,,,BillyDavid:,[3]:11,,21,,,,,31(MW1KD),,NMR,,,,:,,,,,,/[4],,,,NMR(MS),(1HNMR)(13CNMR)(31PNMR)(1HNMR)[5],(),1HNMR,,9514120052(1),;,(metabolicfingerprintanaly2sis),1(NMR)A;BNMR[6],,31PNMR,,P3+Mg2+,,(metabolicprofi2linganalysis),,NMR,:,;;,;(m/e),,(,),,,(2)[7],(),,2NMRMS,,,NMR,,,(GC),(HPLC),(HPCE)NMRMS,,,,,,,,,,,,[8](PCA)[9](PC),,,,(3),,,NMR,,,(,),06JNephrolDialyTransplantVol.14No.1Feb.20053(PCA),12,,,NMRJones[10],,Bollard[11](1HNMR)B6C3F1SD,22,NMR,(HanWistar,GunnSD),[12]Stanley[13]HWNMR,,,,Rikans[14]28F3445;,,,Kishikawa[15],,(PCA)(1HNMR),:,Phipps[16]NMR,,;,Honglian,libitum,NMR,56,,[18](4),4,(NMR),,,NMR,NMR1614120052,,,[19],,GC/MS:3232,;32,NMR,,300,NMR[20],,,,,,,,,,NMR,,,,1992,How2ells[21](1HNMR)(PCA),85%,62%MokaNMR,,,(CHD),X,Brindle[22]X,NMR,,CHD92%,93%(5)CHD,222MAGICAD(),(2000,800),NMR,,5(NMR);,(1H13CNMR),NMR(Reye)(Alzheimer)[23]1HNMR,,,,NMR,;,(FDA)[24]1989,Gartland[25](),1HNMR,(PCA),,,Holmes[26]HgCl2()(),91HNMR,20,,26JNephrolDialyTransplantVol.14No.1Feb.2005,HgCl2;(),,(),;,,1995,Anthony[27]NMR,,18,HolmesNMR,,1310,,727,4(),(HWSD),90%(PCA),,Coen[28],,NMR:,,,,,,,[29],,,,,,,,,,,1GoodacreR.Makingsenseofthemetabolomeusingevolutionarycom2putation:seeingthewoodwiththetrees.JExpBot,2004,0:4312NicholsonJK,TimbrellJA,SadlerPJ.ProtonNMRspectraofuriceasindicatorsofrenaldamage:mercurynephrotoxicityinrats.MolPharamacol,1985,27:6443GermanJB,BaumanDE,BurrinDG,etal.Metabolomicsintheo2peningdecadeofthe21stcentury:buildingtheroadstoindividual2izedhealth.JNutr,2004,134(10):27294DouglasBK.Metabolomicsandsystemsbiology:makingsenseofthesoup.CurOpininMicrobiology,2004,7:2965ChengLL,LenanCL,BogdanovaA,etal.EnhancedresolutionofprotonNMRspectraofmalignantlymphnodesusingmagicanglespin2ning.MagResMed,1996,36:6536,,...2000,40(11):97PaulH,GamacheDF,MeyerMC,etal.Metabolomicapplicationsofelectrochemistry/massspectrometry.JAmSocMassSpectrom,2004,15:17178RobertsonDG,ReilyMD,LindonJC,etal.Metabonomictechnologyasatoolforrapidthroughputinvivotoxicityscreening.CompreToxi,2002,14:5839WatersNJ,HolmesE,WarterfieldCJ,etal.NMRandpatternrec2ognitionstudiesonliverextractsandintactliversfromratstreatedwitha2naphthylisonthiocyanate.BiochemPharmacol,2002,64:6710JonesAR.Someobservationsontheurinaryexcretionofglycinecon2jugatesbylaboratoryanimals.Xenobiotica1982,12:38711BollardME,KeunH,EbbelsT,etal.Comparativemetabonomicsofdifferentialspeciestoxicityofhydrazineintheratandmouse.Toxi2col,2005,inpress.12CostaC,DeAntoniA,BaccichettiF,etal.Metabolitesandenzymeactivitiesinvolvedintryptophanmetabolismintwostrainsofmouse.ItalJBiochem,1984,33(5):31913StanleyEG.1HNMRspectroscopicandchemometricstudiesonen2dogenousphysiologicalvariationinrats.PhDthesis,UniversityofLondon,2002,43.14RikansLE,HornbrookKR,CaiY.Carbontetrachloridehepatotoxici2tyasafunctionofageinfemaleFischer344rats.Mech.Ageing3614120052Dev,1994,76(223):8915KishikawaT,TakahashiH,ShimazawaE,etal.Diurnalchangesincalciumandphosphatemetabolisminrats.HormMetabRes,1980,12:54516PhippsAN,StewartJ,WrightB,etal.Effectofdietontheurinaryexcretionofhippuricacidandotherdietary2derivedaromaticsinrat.Acomplexinteractionbetweendiet,gutmicrofloraandsubstratespe2cificity.Xenobiotica,1998,28(5):52717HonglianS,Vigneau2CallahanKE,ShestopalovAI,etal.Characteri2sationofdiet2dependentmetabolicserotypes:primaryvalidationofmaleandfemaleserotypesinindependentcohortsofrats.JNutr,2002,132:103918ZuppiC,MessanaI,ForniF,etal.1HNMRspectraofnormalu2rines:referencerangesofthemajormetabolites.ClinChimActa,1997,265(1):8519,,.GC2MS.,2004,24(2):21320LindonJC,NicholsonJK,EverettJR.NMRspectroscopyofbioflu2ids.AnnualReportsonNMRSpectroscopy,1999,38:121HoellsSL,MaxwellRJ,PeetAC,etal.Aninvestigationoftumor1Hnuclearmagneticresonancespectrabytheapplicationofchemometrictechniques.MagResMed,1992,28:21422BrindleJT,AnttiH,HolmesE,etal.Rapidandnoninvasivediag2nosisofthepresenceandseverityofcoronaryheartdiseaseusingH212NMRbasedmetabonomics.NatureMedicine,2002,8:14392323LindomJC,NicholsonJK,HolmesE,etal.Theroleofmetabo2nomicsintoxicologyanditsevaluationbytheCOMETproject.ToxiAppliPharm,2003,187:13724RaamsdonkLM,TeusinkB,BroadhurstD,etal.Afunctionalge2nomicsstrategythatusesmetabolomedatatorevealthephenotypeofsilentmutations.NatureBiotechnol,2001,19:4525GartlandKP,BommerFW,NicholsonJK,Investigationsintothebio2chemicaleffectsofregion2specificnephrotoxins.MolPharm,1989,35:24226HolmesE,NicholsonJK,TranterG.Metabonomiccharacterizationofgeneticvariationsintoxicologicalandmetabolicresponsesusingprob2abilisticneuralnetworks.ChemResToxi,2001,14:18227AnthomyML,RoseVS,Nicholson,etal.Classificationoftoxinin2ducedchangesin1HNMRspectraofurineusinganartificialneuralnetwork.PharmaceuticalBiomedicalAnalysis,1995,13:20528CoenM,LenzEM,NicholsonJK,etal.AnintegratedmetabonomicinvestigationofacetaminophentoxicityinthemouseusingNMRspec2troscopy.ChemResToxi,2003,16:295[]2005201218()46JNephrolDialyTransplantVol.14No.1Feb.2005