骨质疏松动物模型建立与评价

12(,100005)1997209218,19972112121,6100412,300052:,,27,;,,,R2332;R3632332;R681A100121978(1999)0520391205()(,)(,),,,,,:;;;;,(),,,,,1941Albright,,,50,,,,,,,,,,,,,,1:;,,:,(vs),(vs)111,,,11111WistarSprague2Dawley,3mon7mon(Sham),(OVX),();2022,;:1111111(1):(E2)(BGP),(FSH)(LH),(RIA);(ALP),AKPALP,(EDTA2Na2),;,EDTA,,,;,3040mgL-1;,,;I(Pro22C),,,,(2):(HOP),193ChinesePharmacologicalBulletin1999Oct;15(5):3915,,,T;,,;,;deoxypyridinoline(Dpyr)pyridinoline(Pyr),,:HPLCEIA,;,,1111112:,;:,,,:X(DEXA),(SPA),(DPA)(QCT),(UltraSonic),111111314d3d,:(),2030mgkg-1BW;(calcein)23d,,,:23mm,,5gL-1Villanueva120h,70%,95%100%,,,,100mOlympusOptonContron,,q,1,2Tab1BonehistomorphometricparametersinundecalcifiedofthefemurDataSymbolUnitBonetotalareaT.Armm2CorticalperiosteallengthP.PmmmCorticalperiosteallengthE.PmmmCorticalendosteallengthMa.Armm2MarrowcavitareaP(E)2sl.PmmmSingle2labeledlengthP(E)2dl.PmmmDouble2labeledsurfaceP(E)2Ir.L.WimOsteoidlengthEr.PmmmOsteoidseamwidthE2O.WimResorptionlengthEr.Pmmm1111114():(MaximumLoad,Fmax,N):,;(Deformation,mm):;(StructuralRigidity,df/dx):;(mj):21111115(-):10%,10%2wk;10%,24h,,6m,,(SiriusRedF3BA2N,MobayChemicalCo.Union,NJ)1h,1h,Tab2DataandcalculationformulaofhistomorphometricinundecalcifiedofthefemurDataSymbolUnitCalculationformulaCorticaltotalareaCt.Armm2T.Ar-M.ArPercentageofcorticalarea%Ct.ArCt.Ar/T.Ar100%Percentageofmarrowcavityarea%Ma.ArMa.Ar/T.Ar100%LabeledlengthP(E)2L.PmmmP(E)-sl.Pm/2+P(E)-dl.PmPercentageoflabeledlengthP(E)2%L.PmP(E)-L.Pm/P(E)-Pm100%MineralappositionrateP(E)2Marm/dP(E)-Ir.L.Wi/markingtimeintervalBoneformationrateP(E)2BFRm/dP(E)-L.PmP(E)-Mar/P(E)-PmPercentageofosteoidlengthE2%O.PmE-O.Pm/E-Pm100%Percentageofrsorptionlength%Er.PmEr.Pm/E-Pm100%RatioofresorptionlengthL.Pm/Er.Pm293ChinesePharmacologicalBulletin1999Oct;15(5)Harris,,,Olympus,11112Swiss2Weber,8wk,twy(tip2toewalkingYoshima),,,11113,,,,11114(Boneremodeling)(Boneturnover),,112,,,,,(Sham),,(OVX):buserelin(),,,(E2);Casodex,,;GnRH(),,,,,,,,,,;,,,,2:,,,;(,),,,,(mountainsheep),(beagledogs):,,,,,34wk,,,,3,,,,(Bonemodeling)(Boneturnover),,,,:3mon,7mon()3mon,3mon,,7mon,,7mon:1mon3mon6mon12mon18mon24mon,13mon,,6mon,12mon,:7mon,,3mon7mon(,),,:,,,,,/,393ChinesePharmacologicalBulletin1999Oct;15(5)3mon7mon,(),;(P0105);(P0101,P0105);,(P0105),7monBGP3mon(P0101);,,?,,SPADPADEXAQCT,,,,,,,;,,,,;,,,,,,,,,,,,,,,,:,,,90%,,,,1JiangY,ZhaoJ,GenantHKetal.Long2termchangesinbonemineralandbiochemicalpropertiesofvertebraeandfemurinaging,dietarycalciumrestricted,and/orestrogen2deprived/replacedrats.JBoneMineralRes,1997;12:820302MostW,SchotL,EderveenAetal.Invitroandinvivoevi2dencethatestrogenssuppressincreasedboneresorptioninducedbyovariectomyorPTHstimulationthroughaneffectonosteoclato2genesis.JBoneMineralRes,1995;10:1523303GouldingA,GoldE.Buserelin2meidatedosteoporosis:effectsofrestoringestrogenonboneresorptionandwholebodycalciumcon2tentintherat.CalcifTissue,1990;46:1494ChowJWM,LeanJM,ChambersTJ.172estradiolstimulatescancellousboneformationinfemalerats.Endocrinology,1992;130:3025325BainSD,BaileyMC,CelinoDLLetal.Highdoseestrogenin2hibitsboneresorptionandstimulatesbonefoormationintheo2variectomizedmouse.JBoneMineralRes,1993;8:435426PiedraC,TorresR,RapadoAetal.Serumtartrate2resistantacidphosphataseandbonemineralcontentinpostmenopausalosteoporo2sis.CalcifTissue,1989;45:58607TobiasJH,ChowJ,ColstonKWetal.Highconcentrationof172estradiolstimulatestrabecularboneformationinadultfemalerats.Endocrinology,1991;128:408128Takano2YamamotoT,RodanGA.Directeffectsof172estradiolontrabecularboneinovariectomizedrats.ProcNatlAcadSciUSA,1990;87:217269ChowJ,TobiasJH,ColstonKWetal.Estrogenmaintainstra2becularbonevolumeinratsnotonlybysuppressionofboneresorp2tionbutalsobystimulationofboneformation.JClinInvest,1992;89:74810ChenMM,YehJK,AloiaJF.Effectsofovariectomyoncancellousboneinthehypophysectomizedrat.JBoneMineralRes,1995;10:13344211WronskiTJ,ClintronM,DohertyALetal.Estrogentreatmentpreventsosteopeniaanddepressesboneturnoverinovariectomizedrats.Endocrinology,1988;123:681612ChristeansenC,ChristeansenMS,LarsenNE.Pathophysiologicalmechanismofestrogenonbonemetabolism:dose2responserelation2shipinearlypostmenopausalwomen.JClinEndocrinolMetab,1982;55:11243013StockJL,CoderreJA,MalleteLE.Effectsofashortcourseofes2trogenonmineralmetabolisminpostmenopausalwomen.JClinEndocrinolMetab,1985;61:59560014GouldingA,GoldE.Anewwaytoinduceosteoporosisintherats:comparisonoftheeffectsofsurgicalovariectomyandadministrat2tionoftheLHRHagonistsbuserelinonboneresorptionandcompo2sition.JEndocrinol,1989;121:2938MethodsofestablishmentandcriterioninanimalmodelsofexperimentalosteoporsisWANGQing,SUNLan,GONGHai2Yang,ZHENGHu,QIUMing2Cai,LIUJing2Sheng(DeptofPharmacology,InstitudeofBasicMedicalSciences,CAMS&PUMC,Beijing100005)ABSTRACTTherearetwomajoranimalmodelsinexperimentalosteoporosis,oneistotal2bodybonemassloss(total2bodyBML),theother,localbonemassloss(localBML).Dependentuponthemethods493ChinesePharmacologicalBulletin1999Oct;15(5)(,200031)R57513;R97119;R34117A100121978(1999)0520395203,,,;;;,[1],,13:2:L2+NADP++H2O2+N