糖皮質(zhì)激素對(duì)神經(jīng)細(xì)胞NMDA受體亞單位基因多信號(hào)調(diào)節(jié)的影響.pdf

1、佳木斯大學(xué)碩士學(xué)位論文糖皮質(zhì)激素對(duì)神經(jīng)細(xì)胞NMDA受體亞單位基因多信號(hào)調(diào)節(jié)的影響姓名：何靜申請(qǐng)學(xué)位級(jí)別：碩士專業(yè)：內(nèi)分泌指導(dǎo)教師：柴國(guó)祿潘佳秋20080606Abstractobjective“Excesso￡91ucoconicoidcausesneuronaldamagewithcognitivedisordersbutthemolecularmechanismremainsunclearInthisstudyweexami—net

2、heeffectofadrenalcorticosteroidsonthetranscriptionofN—methy—Das—partate(NMDA)glutamatereceptorsubunitgenesandAlzheimerdisease(AD)relatedgenessuchasamyloidprecursorprotein(APP)，p—siteamyloidprecursorprotein—cleavingenzyme

3、l(BACE1)，andpresenilinusingneuroblasomacell1inesinvitroMethods：UsingBE(2)M17cell1ine，ahumanneuroblasomacell1ineinwkichthe：5’promoterluciferasefusiongeneisstablyincorporated，weretreatedwiththetestplasmidsNMDAglutamaterece

4、ptorsubunitgenesandAD—relatedgenesforadefindedtimeintervalanddose，andexaminedtheeffectsofglucococorficoidonthemultisignalregulationoftheratNMDA1receptorsubunitgenebya1uciferaseassayendogenousexpressionofthehumanNMDAlmRNA

5、wasexaminedbysemiquantitativeRTPCRUsingNeur02Acell1ine，aratneuroblasomacell1ineinwhichtheglutamateinducedcelltoxicityexperimentwasexamined。byCytoTox96。non—radioactivecytotoxicity，assay。kitResults：Wefoundthatsyntheticgluc

6、ocorticoiddexamethasone(dex)potentlyincreasedthepromoteractivityofNMDAland2Asubunitgenes，butdidnotstimulatethoseofAlzheimer—relatedgenesThesimilareffectofdexwasobservedonintrinsicNMDAlmRNAexpressionFuthermore。dexshowedsy

7、nergisticandadditiveeffectswithproteinkinaseAandC—mediatedsignalingpathways，respectivelyFinallytreatmentoftheNeur02Acells，whichexpressintrinsicglucocorticoidreceptor’withdexsignificantlyenhancedtheglutamate—inducedneurot

8、oxicityConclusion：Ourresultssuggestthatglucocorticoidinducedneuronaldamagemaybe，at1eastpartlyattributabletoenhancedexpressionofglutamateNMDAreceptorwithresultantincreaseinthesusceptibilityofglutamateinducedexcitotoxicity