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1、LifeSciences69(2001)289–299ProtectiveeffectofXY99-5038onhydrogenperoxideinducedcelldeathinculturedretinalneuronsYanXina,b,YuhayT.Fongb,GeraldWolfc,DeliaWolfc,WeiCaod,*aTheInstituteofChongchiTraditionalChineseMedicine,Chongchi,Sichuang,People’sRepublicofChinabAmericanBiologyEngine
2、eringScienceResearchInstitute,Glendale,CA91201,USAcHarvardMedicalSchool,MassachusettsGeneralHospital,Boston,MA02114,USAdDepartmentofOphthalmology,UniversityofOklahomaHealthScienceCenter,OklahomaCity,OK73104,USAReceived10October2000;accepted22November2000AbstractXY99-5038isaprepar
3、ationfromaspecificformulaprovidedbyDr.YanXin,arenownedTradi-tionalChineseMedicinespecialist.Thisformulationhasproventobeeffectivewithoutsideeffectsbuthasnotbeenstudiedunderrigorouslaboratoryconditions.InordertoinvestigatetheroleofXY99-5038inprotectingneuronsfromdegeneration,weused
4、retinalneuronalcultureasamodelsystemtostudytheprotectiveeffectsofXY99-5038againsthydrogenperoxide(H2O2)inducedcytotoxicity.Basicfibroblastgrowthfactor(bFGF),apotentneurotrophicfactor,wasemployedascomparableagent.Reti-nasof0–2daysoldSprague-Dawleyratswereisolated,dissociated,andthe
5、neuronsmaintainedfor2weeksinasyntheticserum-freemedia.CytotoxicitywasdeterminedbyMTT(3,(4,5-dimethylthiazol-2-yl)2,5-diphenyl-tetrazoliumbromide)andLDH(Lactatedehydrogenase)assays,whereasapoptoticcelldeathwasevaluatedbytheTUNEL(TdT-mediateddigoxigenin-dUTPnick-endlabeling)assay.T
6、reatmentwithH2O2significantlyinduceddeathofretinalneurons.PretreatmentwithXY99-5038priortoinsultgreatlyinhibitedorattenuatedH2O2inducedcytotoxicityandapoptosis.Theseeffectswereshowntobedose-dependent.OurdataalsoshowthattheprotectiveeffectofXY99-5038ismorepotentthanthatofbFGF.Ourda
7、tasuggestthatXY99-5038couldbeapotentialagentinthetreatmentofdisordersassociatedwithoxidativedamage.©2001ElsevierScienceInc.Allrightsreserved.Keywords:XY99-5038;Oxidativestress;Hydrogenperoxide;Apoptosis;Neuroprotection;Retinalneuronalcul-ture;YanXinqigong;TraditionalChineseMedici
8、ne;ExternalqiIntroductionOverthepastthre