托吡酯對(duì)大鼠局灶性腦缺血再灌注保護(hù)作用的研究.pdf

1、朱曉峰托吡酯對(duì)大鼠局灶性腦缺血再灌注保護(hù)作用的研究托吡酯對(duì)大鼠局灶性腦缺血再灌注保護(hù)作用的研究摘要目的：本文旨在探索抗癲癇類藥物托吡酯對(duì)大鼠局灶性缺血損傷的保護(hù)作用及其相關(guān)機(jī)制。通過(guò)線栓法構(gòu)建SD大鼠局灶性腦缺血再灌注模型，并用托吡酯干預(yù)，24h后進(jìn)行神經(jīng)功能評(píng)分，檢測(cè)缺血再灌注后SD大鼠腦缺血梗死體積、SD大鼠缺血半球腦組織含水量以及腦組織缺血梗死區(qū)的氨基酸類神經(jīng)遞質(zhì)(GABA、Glu)含量；并觀察腦梗死中心區(qū)及缺血半暗帶的小膠質(zhì)細(xì)胞

2、及星形膠質(zhì)細(xì)胞形態(tài)；為更好的指導(dǎo)腦梗死后合并癲癇的臨床治療及擴(kuò)大抗癲癇藥物適應(yīng)癥提供實(shí)驗(yàn)支撐。方法：將成年雄性SD大鼠隨機(jī)的分為三組，分別為單純?nèi)毖俟嘧⒔M、托吡酯(Topir鋤ate，TPM)干預(yù)組和假手術(shù)組，每組28只。利用線栓法構(gòu)建SD大鼠大腦中動(dòng)脈閉塞(MCAO)再灌注模型，TPM干預(yù)組動(dòng)物于插線前3天每天予以新鮮配置的托吡酯混懸液(8mg／ml，80mg／kg)灌胃，假手術(shù)組和單純?nèi)毖俟嘧⒔M予以生理鹽水10ml／kg灌胃。缺

3、血再灌注后24h時(shí)進(jìn)行神經(jīng)功能評(píng)分，后處死動(dòng)物，測(cè)定梗死體積、腦含水量，高效液相色譜分析儀測(cè)腦組織內(nèi)GABA、Glu的含量，利用免疫組織化學(xué)染色觀察腦梗死中心地帶及缺血半暗帶的小膠質(zhì)細(xì)胞及星形膠質(zhì)細(xì)胞形態(tài)。結(jié)果：(1)假手術(shù)組SD大鼠未發(fā)現(xiàn)神經(jīng)功能缺損現(xiàn)象：?jiǎn)渭內(nèi)毖俟嘧⒔M神經(jīng)功能評(píng)分為147085；TPM干預(yù)組神經(jīng)行為學(xué)評(píng)分為286i096，單純?nèi)毖俟嘧⒔M和托吡酯干預(yù)組相比有統(tǒng)計(jì)學(xué)意義(氏005)。(2)通過(guò)TTC染色發(fā)現(xiàn)假手術(shù)組并

4、無(wú)缺血梗死灶；單純?nèi)毖俟嘧⒔M梗死體積百分比為(3528924)％；托吡酯干預(yù)組梗死體積百分比為(8364452)％，單純?nèi)毖俟嘧⒔M和托吡酯干預(yù)組相比有顯著性差異(p005)。(4)大鼠腦皮層組織Glu、GABA含量分別為：假手術(shù)組(8s374577)umol／L、(5584084)umol／L；單純?nèi)毖俟嘧⒔M(1057842088)umol／L、(837155)umol／L；TPM干預(yù)組(7266士998)umol／L、(1188

5、254)umol／L。單純?nèi)毖俟嘧⒔MSD大鼠缺血梗死的皮層組織朱曉峰托吡酯對(duì)大鼠局灶性腦缺血再灌注保護(hù)作用的研究3TheNeuroprotectionofTopiramateinRatsModelsofFocalIschemia—ReperfusionandtheNeuroprotectiveMechanismAbstractobjeetive：Inthisstudytheneuronalprotectivemechanismofto

6、piramate(TPM)wereobservedbyratfocalcerebralischemiareperfusionmodelmiddlecerebralarteryocclusion(MCAO)Itwasmeasuredthenervefunctiondeficiencyscores，infarctionvolume，estimatedbrainwatercontentandthecontentofaminoacidsofce

7、rebralcodexinthebothTPMtreatedandMCAOgroupItwasobservedchangeofmicrogliaandastrocytesactivationintheTPMtreatedgroupcomparedtotheMCAOgroupMethods：HealthyMaleSDratswererandomlyassignedtoshamgroup、MCAOgroupandTPMMCAOgroupTh

8、entheyweresubjectedtoleftmiddlecerebralarteryocclusionfor2handreperfusionfor24hRatsintheTPMMCAOgroupwereinjectedTPMsuspension(8mg／ml，80mg／kg)3daysbeforetheinitiationofthearteryocclusionandthereperfusionThenervefunctionde

9、ficiencyscoresweremeasuredEstimatedbrainwatercontentbyweighingmethodTheinfarctvolumewasevaluatedthroughTTCstainingEstimatedthecontentofaminoacidsofcerebralcortexbythemethodofhighperformanceliquidchromatography(HPLC)withf

10、luorescentdetectionAtlastweobservedmicrogliaandastrocytestypesinthecenteroftheinfarctsandincerebralischemicpenumbrabyimmunohistochemicalstainingResult：(1)Theshamgroupdidnothaveneurologicdeficits；ThescoresoftheMCAOgroupwe

11、rel47士085；ThescoresoftheTPMMCAOgroupwere286士096ThereweresignificantdifferencesontheneurologicalimpairmentscoresbetweentheTPMMCAOgroupandtheMCAOgroup(P005)(2)ThepercentageofinfarctvolumeintheMCAOgroupwas3528t924，thoseofth

12、eTPMMCAOtreatedgroupwas836t452Therearesignificantdifferencesbetweentwogroups伊O05)(3)Thebrainwatercontentwas(7558士284)％inshamgroup；(8585士2：75)％inMCAOgroup；(7954士156)％inTPMMCAOgroupTPMMCAOgroupobviouslyreducewatercontentin