EGCG對鉛致大鼠海馬神經(jīng)元突觸可塑性和氧化損傷的修復作用及機制.pdf

1、中國科學技術大學博士學位論文EGCG對鉛致大鼠海馬神經(jīng)元突觸可塑性和氧化損傷的修復作用及機制姓名：尹述婷申請學位級別：博士專業(yè)：神經(jīng)生物學與生物物理學指導教師：阮迪云20090401AbStraCtReeentStudieshaveshownthatleadcausesoxidativesnessbyinducingmegenerationofreactiveoxygenSpecies(ROS)aIldreducingthea11tio

2、xidantdefensesystemofcells，whichsuggestsmatantioxidantSmayplayanimponantroleinⅡletrea：tIllentofleadpoisoningAsakindofexcellentscaVengeroffreeradicaJs，modulatorofimmmlesyStems‘a(chǎn)11dchelatorofhea、，)，metal，、VhetherEp追allocat

3、ecllin一3gallate(EGCG)haVetheprotectiVee虢ctsonalteredoxidatiVeStresspar鋤eteraRerleadtreatmentinvivoandinvitrosystemsremainSunclearThepresentstudy、Ⅳasdesignedt0elucidatewhetherEGCGhaveanyprotectiVee毹Cts0ntheacc啪ulationofRO

4、SauldadecreaSeofmitochondrialmembranepotential(4掣乙)inleadexposedculturesofhippoc鋤palneuronsandwhetherEGCGcouldreVersethechaIlgesonredoxstatesi11rathippocampuscausedbyleadexposureOurresultssho、Ⅳedtllatglutamione(GSH)andsu

5、peroxidedismutase(SOD)actiVit)rdecreasedaccompaniedwithLTP鋤plitlldedecreaseinCAlareaofhippocampusinmeleadexposed伊oupEGCGsupplementationfollo謝ngleadintoxicationresultedinincreasesiIltIleGSH觚dSOD1evelsandincreaSesintheLTP鋤

6、plitudeMalondialdehyde(MDA)levels，am萄orlipidperoxidationbyproduct，increaSedfollowingleadexposureanddecreaSedfollowingEGCGtreatmentInhippoc鋤palneuronculturemodel，leadexposure(20pM)sign鹼cantlyinhibitedtheViabili夠ofneuronsw

7、hichwaSfolIowedbvanaccumulationofROSandadecreaseof么掣‰TreatmentbyEGCG(1050山田e插：ctivelyincreausedceUViability，decreaSedROSfo姍ationandimproved么‰inhippoc啪palneuronsexposedtoleadTheseobservationssuggeStthatEGCGisapotentialcom

8、plementaryagentinthetreatrnentofchronicleadintoxicationthrou曲itsantioxidatiVecharacterOurpreviousstudyshowedthatEGCGhaSprooxidantefrectsath追hconcelltrationThus，inthisstudy，wetriedtoexaminethepossiblepathwayofEGCGinducedc

9、elldeathinculturesofrathippocampalneu】舊nsOurresultsshowedmatEGCGcausedarapidelevationofintracellularfreecalcium1evels(【Caz】j)inadosedependentwayE)【posuretoEGCGdoseandtime—dependentlyiIlcreasedtheproductionofROSandreduced

10、4％l2uswenaStheBcl一2／BaXexpressionratioImport砒ltly，BAPTAAM，EGTAandvit鋤inEcouldattenuateBGCGinduced￡巾optoticresponses，includingROSgeneration，mitochondrialdysfunction，andfinallyp叭iallypreventedEGCG—inducedceUdeathFunhennore