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1、生理学报ActaPhysiologicaSinica,June25,2007,59(3):285-292285http://www.actaps.com.cn研究论文青藤碱对吗啡依赖与戒断小鼠小脑与脊髓NO/nNOS系统的影响刘珍1,**，郑济芳2,**，杨露青2，易岚2，胡弼1,*南华大学1生理学教研室；2遗传学教研室，衡阳421001摘要：本文旨在探讨青藤碱对吗啡依赖与戒断小鼠的小脑和胸腰段脊髓中一氧化氮(nitricoxide,NO)/神经元型一氧化氮合酶(neuralnitricoxidesynthase,nNOS)系统的影响及作用机制。采用吗啡剂量递增法建立小鼠吗啡
2、依赖模型，用纳洛酮激发戒断症状，评价小鼠急性戒断时齿颤、扭体、直立、喷嚏、眼睑下垂等戒断症状，对成瘾小鼠用青藤碱(40mg/kg,i.p.)治疗后，再用纳洛酮激发观察戒断症状。半定量RT-PCR检测小鼠小脑和胸腰段脊髓nNOSmRNA表达变化，化学比色法和硝酸还原酶法分别测定小鼠小脑和胸腰段脊髓组织匀浆的nNOS活性与NO含量。结果显示：(1)青藤碱可以扭转由吗啡依赖引起的小鼠体重下降的趋势，减轻小鼠急性戒断时齿颤、扭体、直立、喷嚏、眼睑下垂等戒断症状；(2)青藤碱可降低小鼠吗啡依赖与戒断时在小脑与胸腰段脊髓中异常上调的nNOSmRNA水平，使酶活性下降到接近对照组水平。nN
3、OS催化产生的NO含量与酶活性的变化一致；(3)单独使用青藤碱，小鼠没有出现类似吗啡引起的戒断症状，小脑与胸腰段脊髓中nNOSmRNA水平及酶活性没有异常升高。上述结果表明，青藤碱本身无成瘾性，但能显著减轻吗啡依赖小鼠的戒断征状，其作用机制可能与青藤碱影响小脑与脊髓中的NO/nNOS系统有关。关键词：青藤碱；吗啡；戒断；一氧化氮合酶中图分类号：Q426EffectsofsinomenineonNO/nNOSsystemincerebellumandspinalcordofmorphine-dependentandwithdrawalmiceLIUZhen1,**,ZHENGJ
4、i-Fang2,**,YANGLu-Qing2,YILan2,HUBi1,*1DepartmentofPhysiology;2DepartmentofGenetics,NanhuaUniversity,Hengyang421001,ChinaAbstract:Toexploretheeffectofsinomenineonthenitricoxide(NO)/neuralnitricoxidesynthase(nNOS)systeminthecerebellumandspinalcordofmorphine-dependentandmorphine-withdrawalKun
5、mingmice,miceweresubjectedtoinjectionofmorphinewithanincreasingdosefor5d,andthenweretreatedwithsinomenine(40mg/kg,i.p.)foranother5d.Naloxonewasusedtodevelopacutewithdrawal,andthewithdrawalsyndromes,includingteethchattering,twisting,straightening,sneezingandptosis,wereinvestigated.nNOSmRNAex
6、pressionsinthecerebellumandspinalcordweredeterminedbysemi-quantitativeRT-PCR.nNOSactivityandNOlevelweredeterminedbythechemistry-colorimetryandnitratereductase-reduction,respectively.Theresultsobtainedwereasfollows:(1)Sinomeninerestoredthedecreaseinbodyweightandalleviatedthesignsofmorphine-w
7、ithdrawalinmice.(2)SinomeninealsoreducedtheincreasesinnNOSmRNAexpressionandnNOSactivityresultingfrommorphine-dependence,andsimultaneouslyattenuatedthehighlevelofNOinbothtissuesfollowingmorphine-withdrawal.(3)Administrationofsinomeninealonedidnotdevelopph
