不同剂量异丙酚复合电休克治疗对抑郁大鼠行为学及海马突触素的影响重庆医科大学附属第一医院麻醉科400016刘媛媛闵苏董军曹俊黎平刘永峰【摘要】目的探讨不同剂量异丙酚复合电休克治疗对抑郁大鼠行为学改变及海马突触素(SYP)表达的影响。方法成年健康雄性SD大鼠50只，体重200～250g，随机分为5组(n=10)：正常对照组(C组)、抑郁组(D组)以及不同剂量异丙酚联合电休克组，其中包括低剂量组(M1组)、中剂量组(M2组)、高剂量组(M3组)。采用孤养加慢性不可预见轻度应激(CUMS)建立抑郁模型，建模成功后，C组、D组腹腔注射生理盐水10ml/kg，于大鼠双颞侧安放电极但不实施电休克处理，M1、M2、M3组分别腹腔注射异丙酚90mg/kg、110mg/kg、130mg/kg，待翻正反射消失后，将电极安放于大鼠双颞侧，行电休克处理(50mA、50Hz、单个正弦半波刺激20ms、持续50次)，引起强直-阵挛抽搐发作。以上处理每天一次，连续7d，一共7次。建模前后及处理后1天均对大鼠进行openfield测试和糖水消耗实验。测试结束后1天内处死大鼠，采用免疫组织化学法检测大鼠海马CA3区SYP蛋白的表达，RT-PCR法检测大鼠海马SYPmRNA的相对表达量。结果建模后，与C组比较，其余4组水平计分、垂直计分、理毛次数减少，中央格停留时间延长，糖水消耗百分比下降(P＜0.05)。电休克治疗后，与D组比较，M1、M2组水平计分、垂直计分、理毛次数增加，中央格停留时间减少，糖水消耗百分比升高，SYP蛋白及其mRNA表达水平升高(P＜0.05)，M3组各项行为学评分与SYP表达差异均无统计学意义(P>0.05)；与M1组比较，M3组水平计分、垂直计分、理毛次数减少，中央格停留时间增加，SYP蛋白及其mRNA表达水平降低(P＜0.05)。结论90mg/kg、110mg/kg异丙酚复合电休克治疗对抑郁大鼠有一定疗效，而130mg/kg异丙酚复合电休克治疗对抑郁大鼠的疗效不佳，其机制可能与大剂量异丙酚过度抑制大鼠电休克后海马SYP表达有关。【关键词】二异丙酚；电惊厥疗法；抑郁症；突触素EffectofdifferentdosesofpropofolonethologyandsynaptophysininhippocampusofdepressedratsafterelectroconvulsivetherapyLIUYuan-yuan,MINSu,DONGJun,etal.DepartmentofAnesthesiology,FirstAffiliatedHospitalofChongqingMedicalUniversity,Chongqing400016,ChinaCorrespondingauthor:MINSu(E-mail:minsu89011068@yahoo.com.cn)[Abstract]ObjectiveToinvestigatetheeffectofdifferentdosesofpropofolonethologyandtheexpressionofmRNAandproteinofsynaptophysin(SYP)inhippocampusofdepressedratsafterelectroconvulsivetherapy(ECT).MethodsFiftyadultmaleSDratsweighing200～250gwererandomlydividedintofivegroups(n=10each):onecontrolgroup(C),onementaldepressiongroup(D)andthreedifferentdosesofpropofolcombinedwithelectroconvulsivetherapygroup(M1,M2,M3).Chronicunpredictablemildstress(CUMS)modelwasestablishedingroupsexceptgroupC.TheratsingroupM1,M2andM3receivedintraperitoneal(IP)propofol90、110and130mg/kgrespectively+ECTonceadayfor7times,whereastheratsingroupCandDreceivedIPnormalsalineinsteadofpropofol.TheratsunderwentopenfieldtestandsucroseliquidconsumptiontestthedaybeforeandafterCUMSmodelestablishedandonedayaftertreatment.Theratswerekilledwithin24hafterthelasttestfordeterminationoftheexpressionofSYPprotein(usingimmuno-histochemistry)andmRNA(usingRT-PCR)inthehippocampus.ResultsTheambulationscores,rearingscores,groomingtimesandsucroseconsumptionpercentageweresignificantlydecreasedwhilethecentergriddetentiontime(CDT)wassignificantlyincreasedinothergroupsascomparedwithgroupCaftermodelestablished.Theambulationscores,rearingscores,groomingtimes,sucroseconsumptionpercentage,SYPproteinandmRNAexpressionweresignificantlyincreasedwhileCDTwassignificantlydecreasedingroupM1andM2ascomparedwithgroupD.Theambulationscores,rearingscores,groomingtimes,sucroseconsumptionpercentage,SYPproteinandmRNAexpressionweresignificantlydecreasedwhileCDTwassignificantlyincreasedingroupM3ascomparedwithgroupM1.Conclusion90mg/kg、110mg/kgpropofolcombinedwithECThavetherapeuticeffecttodepressedrats,whereas130mg/kgpropofolcombinedwithECTdonot,whichmayduetohighdoseofpropofolexcessivelyinhibitSYPexpressioninhippocampusofdepressedratsafterECT.[Keywords]Propofol;Electroconvulsivetherapy;Depressivedisorder;Synaptophysin
