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《神經(jīng)活性甾體別孕烯醇酮對(duì)腦皮質(zhì)神經(jīng)元損傷的保護(hù)作用》由會(huì)員上傳分享，免費(fèi)在線(xiàn)閱讀，更多相關(guān)內(nèi)容在行業(yè)資料-天天文庫(kù)。
1、中國(guó)應(yīng)用生理學(xué)雜志,2011,27(2)175*神經(jīng)活性甾體別孕烯醇酮對(duì)腦皮質(zhì)神經(jīng)元損傷的保護(hù)作用李賢慧,張新昌,王剛,劉海玲,夏時(shí)海(武警醫(yī)學(xué)院分子生物學(xué)教研室,天津300162)摘要目的:利用N甲基D天門(mén)冬氨酸(NMDA)誘發(fā)新生小鼠腦皮質(zhì)神經(jīng)元損傷模型,探討神經(jīng)活性甾體別孕烯醇酮對(duì)腦皮質(zhì)神經(jīng)元的保護(hù)作用及其機(jī)制。方法:應(yīng)用RTPCR和Westernblot法檢測(cè)別孕烯醇酮對(duì)2氨基丁酸受體(2GABAR)表達(dá)和對(duì)蛋白激酶B(PKB,又稱(chēng)為Akt)磷酸化的影響。應(yīng)用Western
2、blot和DNALadder方法檢測(cè)NMDA誘發(fā)的神經(jīng)元凋亡及別孕烯醇酮對(duì)NMDA誘發(fā)凋亡的影響。結(jié)果:Westernblot和RTPCR分析表明0.666510mol/L510mol/L別孕烯醇酮使Akt磷酸化增加并促進(jìn)2GABARmRNA的表達(dá)。110mol/L別孕烯醇6酮預(yù)處理小鼠腦皮質(zhì)神經(jīng)元有抗凋亡作用,但510mol/L別孕烯醇酮預(yù)處理小鼠腦皮質(zhì)神經(jīng)元使NMDA誘發(fā)的DNALadder減弱明顯,并能有效抵抗NMDA誘發(fā)的活化型PRAP、Caspase3、Caspase9
3、的增加。結(jié)論:別孕烯醇酮可通過(guò)促進(jìn)2GABAR表達(dá)和增加Akt磷酸化抵抗NMDA誘發(fā)的腦皮質(zhì)神經(jīng)元凋亡。關(guān)鍵詞神經(jīng)活性甾體;別孕烯醇酮;細(xì)胞凋亡;腦皮質(zhì)神經(jīng)元中圖分類(lèi)號(hào)R285.5文獻(xiàn)標(biāo)識(shí)碼A文章編號(hào)10006834(2011)0217504EffectsofneuroactivesteroidallopregnanoloneonthedamageofcorticalneuronsLIXianhui,ZHANGXinchang,WANGGang,LIUHaili
4、ng,XIAShihai(DepartmentofMolecularBiology,MedicalCollegeofChinesePeopleSArmedPoliceForce,Tianjing300162,China)ABSTRACTObjective:ToinvestigatetheprotectivemechanismofneuroactivesteroidallopregnanoloneonNmethylDaspartate(NMDA)inducedtoxicityinprimarymous
5、ecorticalneurons.Methotls:Primaryculturedmousecorticalneuronsweresubjectedtoallopregnanolone,theexpressionofaminobutyricacidreceptor2subunit(2GABAR)mRNAswasdetectedbyRTPCRandAktphosphorylationwasassayedbyWesternblotusingAktphosphoserine473specificant
6、ibody.AftertheculturedmousecorticalneuronswerepretreatedwithorwithoutallopregnanolonepriortotreatmentwithNMDA,DNAisolatedwasanalyzedbyagarosegelelectrophoresisandproteinscollectedwereanalyzedbyWesternblotwithanticleavedPARP,anticleavedcaspase3,andanticl
7、eavedcaspase9antibodies.Results:Whenculturedmousecorticalneuronswereexposedtoallopregnanoloneboththeexpressionof2GABARmRNAsandAktphosphorylationincreased.AllopregnanoloneinhibitedtheNMDAinducedapoptosisanddecreasedthelevelofactivePARP,activecaspase3a
8、ndactivecaspase9notablyatafinalconcen6trationof510mol/L.Conclusion:PretreatmentwithallopregnanolonemaybeneuroprotectiveonNMDAinducedneuronalcellsapoptosisbyincreasing2GABARexpres
