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過氧化物還原酶6敲除減輕癲癇大鼠海馬區(qū)神經(jīng)元損傷

發(fā)布時間:2025-02-09 15:00
  癲癇是一種神經(jīng)系統(tǒng)疾病,其特征在于中樞神經(jīng)系統(tǒng)的興奮性和抑制性神經(jīng)遞質(zhì)失衡引起的神經(jīng)元異常放電。其發(fā)病機(jī)制非常復(fù)雜,與神經(jīng)遞質(zhì)失衡,氧化應(yīng)激和免疫炎癥關(guān)系密切。氧化應(yīng)激會產(chǎn)生大量氧自由基,在正常的生理條件下,機(jī)體會利用和消除多余的自由基,然而,過量的有害刺激,如癲癇會導(dǎo)致組織和細(xì)胞缺氧,損傷甚至壞死。據(jù)報道,在海人酸(Kainic acid,KA)誘導(dǎo)的大鼠癲癇模型中發(fā)現(xiàn)氧化應(yīng)激損傷,并分布在大腦的所有區(qū)域。過氧化物還原酶6(peroxiredoxin6,PRDX6)屬于巰基特異性過氧化物還原酶家族中的一員,含有兩個結(jié)構(gòu)功能域,分別是具有抗氧化功能的過氧化物還原酶活性和促進(jìn)炎癥發(fā)生的非鈣依賴性磷脂酶A2的活性。因此,PRDX6一方面能通過消除活性氧(reactive oxygen species,ROS),參與過氧化細(xì)胞膜的修復(fù)和細(xì)胞磷脂的轉(zhuǎn)運,在抗氧化應(yīng)激中發(fā)揮重要作用;另一方面,能通過其磷脂酶A2的活性促進(jìn)炎癥發(fā)生。2008年Myung-Jeom Ryu等人在Neurochem上發(fā)表了一篇關(guān)于stargazer(stg)突變小鼠表型的文章,該突變小鼠中表達(dá)鈣通道γ2亞基stargaz...

【文章頁數(shù)】:81 頁

【學(xué)位級別】:碩士

【部分圖文】:

圖1PRDX6在KA誘導(dǎo)的癲癇大鼠的外周血及海馬中表達(dá)上調(diào)Fig1PRDX6isupregulatedinhippocampusofKA-inducedseizurerats

圖1PRDX6在KA誘導(dǎo)的癲癇大鼠的外周血及海馬中表達(dá)上調(diào)Fig1PRDX6isupregulatedinhippocampusofKA-inducedseizurerats

安徽醫(yī)科大學(xué)碩士學(xué)位論文27圖1PRDX6在KA誘導(dǎo)的癲癇大鼠的外周血及海馬中表達(dá)上調(diào)Fig1PRDX6isupregulatedinhippocampusofKA-inducedseizurerats(A)SeizuresineachSDratwererecordedusing....


圖2PRDX6在癲癇大鼠腦星形膠質(zhì)細(xì)胞中表達(dá)上調(diào)Fig2PRDX6expressionwasup-regulatedinbrainastrocytesofepilepticrats(A)Co-localizationofPRDX6(red)andGFAP(green)incerebralhippocampus,cortex,lateralventricle.(B)Co-localizationofPRDX6(red)andGFAP(green)inCA1,

圖2PRDX6在癲癇大鼠腦星形膠質(zhì)細(xì)胞中表達(dá)上調(diào)Fig2PRDX6expressionwasup-regulatedinbrainastrocytesofepilepticrats(A)Co-localizationofPRDX6(red)andGFAP(green)incerebralhippocampus,cortex,lateralventricle.(B)Co-localizationofPRDX6(red)andGFAP(green)inCA1,

安徽醫(yī)科大學(xué)碩士學(xué)位論文28圖2PRDX6在癲癇大鼠腦星形膠質(zhì)細(xì)胞中表達(dá)上調(diào)Fig2PRDX6expressionwasup-regulatedinbrainastrocytesofepilepticrats(A)Co-localizationofPRDX6(red)andGFA....


圖3在KA誘導(dǎo)的癲癇鼠腦中,PRDX6不在小膠質(zhì)細(xì)胞以及神經(jīng)元中表達(dá)Fig3PRDX6isnotexpressedinactivatedmicrogliaandneuronsinKA-inducedseizurerats(A)Co-localizationofPRDX6(red)andIba-1(green)inCA3ofthehippocampus.(B)

圖3在KA誘導(dǎo)的癲癇鼠腦中,PRDX6不在小膠質(zhì)細(xì)胞以及神經(jīng)元中表達(dá)Fig3PRDX6isnotexpressedinactivatedmicrogliaandneuronsinKA-inducedseizurerats(A)Co-localizationofPRDX6(red)andIba-1(green)inCA3ofthehippocampus.(B)

安徽醫(yī)科大學(xué)碩士學(xué)位論文29NeuN是成熟神經(jīng)元的標(biāo)記物,我們通過NeuN與PRDX6雙標(biāo),結(jié)果顯示PRDX6(紅)與NeuN(綠)沒有共定位,表明PRDX6也不在神經(jīng)元中表達(dá)(圖3B)。圖3在KA誘導(dǎo)的癲癇鼠腦中,PRDX6不在小膠質(zhì)細(xì)胞以及神經(jīng)元中表達(dá)Fig3PRDX6isn....


圖4在癲癇鼠腦中,iNOS和4-HNE表達(dá)在星形膠質(zhì)細(xì)胞內(nèi)并與PRDX6共定位Fig4OxidativestressmarkersiNOSand4-HNEwereexpressedinastrocytesofepilepsyratsandco-localizedwithPRDX6.(A)Co-localizationofGFAP(red)andiNOS(green)inCA1ofthehippocampus.(B)

圖4在癲癇鼠腦中,iNOS和4-HNE表達(dá)在星形膠質(zhì)細(xì)胞內(nèi)并與PRDX6共定位Fig4OxidativestressmarkersiNOSand4-HNEwereexpressedinastrocytesofepilepsyratsandco-localizedwithPRDX6.(A)Co-localizationofGFAP(red)andiNOS(green)inCA1ofthehippocampus.(B)

安徽醫(yī)科大學(xué)碩士學(xué)位論文30顯示,iNOS(綠)和4-HNE(黃棕)均表達(dá)在GFAP(紅)陽性細(xì)胞內(nèi)(圖4A和B)。與PRDX6共定位,提示癲癇能誘導(dǎo)星形膠質(zhì)細(xì)胞中氧化應(yīng)激水平上調(diào)。圖4在癲癇鼠腦中,iNOS和4-HNE表達(dá)在星形膠質(zhì)細(xì)胞內(nèi)并與PRDX6共定位Fig4Oxidat....



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