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1、VPA解除Met对大鼠皮质神经元GAD表达的抑制-374??论着?中华tt学研究杂志Jo唧a1nfchineseMediciⅡeResearch2006年第6卷第4期VPA解除Met对大鼠皮质神经元GAD表达的抑制张旭,向丽,胡蝉丽【摘要】目的研究丙戊酸(VPA),蛋氨酸(Methionine,Met)对大鼠皮质神经元谷氨酸脱羧酶(GAD)表达的影响,探讨VPA对精神分裂症的治疗作用.方法采用原代培养技术分组培养大鼠皮质神经元,收集细胞,制备GAD粗酶提取液,用比色法测定粗酶提取液GAD活力;分
2、析空白组(无血清培养液),Met组(无血清培养液含终浓度为2mM的Met培养3天后换以无血清培养液),VPA组(无血清培养液含终浓度为2mM的Met培养3天后换以终浓度为0.5mM的VPA无血清培养液)的GAD活性.结果Met组GAD平均酶活力明显低于空白组,差异有统计学意义,而VPA组的GAD平均酶活力接近于空白组,差异无统计学意义.结论蛋氨酸抑制大鼠皮质神经元表达GAD,降低GABA的合成;VPA促进皮质神经元表达GAD,可以使被Met抑制的GAD恢复到正常水平.【关键词】丙戊酸;蛋氨酸;谷
3、氨酸脱羧酶;精神分裂症【中图分类号】R一332【文献标识码】A【文章编号】1680—6115(2006)04—0374—03ValproaterenewGADexpressionwhichhadbeeninhibitedbymethionineinmouseprimarycorticalculturesZHANCXu,XIANGLi,HUChart一DepartmentofBiochemistry,MedwaZSchoof,ZhengZhouUniversity,Zhengzhou450052,
4、China【Abstract】ObjectiveTostudyvalproateandmethionine(Met)regulateglutamicaciddecarboxylase(GAD)ex.pressioninmouseprimarycorticalculturesnouron,investigatethemechanismoftheVPA'Sfunctioninthetreatmentofschizophrenia.MethodsAdoptingprimarycorticalcultu
5、restechniqueculturesneuron,collectecells,lysiscells,usecolorimetricmethodtomeasureGADactivities;ana1)seGADactivitiesofthevacancygroup(sel3.11TI—freeDMEM).theMetgroup(cultureswereincubatedwithMetatafinalconcentrationof2mMinseruITl—freeDMEMfor3days,aft
6、erthatchangeitwithselMIll—freeDMEM),and廿1eVPAgroup(cultureswereincubatedwithVPAatafinalconcentrationof2mMinDMEMafterthatincubatedwithMetatafinalconcentrationof2mMinserum—freeDMEMfor3days).ResultsIntheMetgrDllptheaverageactivitiesofGADisobviouslylower
7、thantheothertwogroup,thedifferencehasstatisticalmeaning.IntheVPAgrouptheaverageactivitiesofGADisapproachtovacancygroup.thedifferencehasn'tstatisticalmeaning.ConclusionThemethionineinhibitsthecorticalneuronexpressGAD.decreas.esGABAsynthesize.,I11eVPAp
8、romotesthecorticalneumnexpressionGAD.andrenewsGADexpressionwhichhadbeeninhibitedbyMetinmouseprimarycomcalcultures.【Keywords】valproate;methionine;glutamicaciddecarboxylase(GAD);schizophrenia增加蛋氨酸(Methlonine,Met)的摄入量,会造成近百分之七十的精神分裂症(schizophrenia,SZ)患者