机构地区:[1]首都医科大学宣武医院药理研究室,北京市100053 [2]中国医学科学院基础所药理室,北京市100005
出 处:《中国临床康复》2004年第28期6274-6276,共3页Chinese Journal of Clinical Rehabilitation
基 金:北京市自然科学基金(7982006)~~
摘 要:背景:参乌胶囊是由首都医科大学宣武医院药理研究室自行研制用于治疗老年痴呆的纯中药制剂,对多种拟痴呆模型动物的学习记忆能力有很好的改善作用。目的:观察拟杭廷顿病(Huntingtondisease,HD)模型大鼠学习记忆能力改变及参乌胶囊对其的干预作用,探讨其可能的作用机制。设计:随机对照的实验研究。地点和材料:实验地点:首都医科大学宣武医院药物研究中心。雄性SD大鼠60只,随机分为正常对照组,3-硝基丙酸(3-nitropropionicacid,3-NPA)模型组,参乌胶囊小剂量、中剂量和大剂量组,氟哌啶醇组。每组10只。在实验进行中,正常对照组死亡1只,3-NPA模型组和参乌胶囊小剂量组各死亡2只,氟哌啶醇组死亡3只,考虑死亡原因为吸入性窒息。干预:3-NPA模型组用3-NPA20mg/kg对SD大鼠隔日腹腔注射1次,共20d,建立拟HD大鼠模型。造模的同时,参乌胶囊小剂量(0.45g/kg)组,中剂量(0.9g/kg)和大剂量(1.8g/kg)组大鼠给予参乌胶囊连续灌胃25d。氟哌啶醇组自造模当日起给予氟哌啶醇,起始剂量为100μg/(kg·d),隔日递增,直至1000μg/(kg·d)。主要观察指标:大鼠在Morris水迷宫中的游出时间和距离;在避暗实验中的潜伏期和错误次数;海马处胆碱乙酰基转移酶活性;大鼠海马CA4区胶质细胞源性神经生长因子的细胞数量及细胞面积。结果:Morris?BACKGROUND:ShenwucapsuleisapuretraditionalChinesemedicinedevelopedbythePharmacologyResearchDepartmentofXuanwuHospitalofCapitalUniversityofMedicalSciences(CUMS).Itisservedtotreatsenialdementiaandhasbeenprovedtobeeffectiveinimprovingthelearningandmemoryabilityofmanykindsofanimalmodelswithdementia.OBJECTIVE:ToobservethechangesoflearningandmemoryabilityofmodelratswithHuntingtondisease(HD),theeffectsofshenwucapsuleonitandexploreitspossiblemechanism.DESIGN:Arandomizedandcontrolledtrial.SETTINGandMATERIALS:ThetrialwasconductedatthePharmacologi-calResearchCenterofXuanwuHospitalofCUMS.Thematerialswere60maleSDratsofcleargrade.Theratsweredividedintothefollowinggroups:Controlgroup,3-nitropropionicacid(3-NPA)group,low-dose,middle-dose,andhigh-doseshenwucapsulegroups,haloperidolgroup,andtherewere10ratsineachgroup.Intheprocessofthetrial,therewere1ratincontrolgroup,2in3-NPAgroupandlow-doseshenwucapsulegrouprespectively,3inholoperidolgroupdied.Thecausemightbeinhalationasphyxia.INTERVENTIONS:20mg/kg3-NPAwasinjectedintraperitonealyineachrateveryotherdayfor20daystomakeHDmodel.Ratsinshenwucapsulesoflowdose(0.45g/kg),middledose(0.9g/kg)andhighdose(1.8g/kg)werefedintragastricallyfor25daysincorrespondinggroups.RatsinhaloperidolgroupwerefedwithhaloperidolfromthedaytheHDmodelratsweremade.Theinitialdosewas100μg/kgperday,whichwasincreasedeveryotherdaytill1000μg/kgperday.MAINOUTCOMEMEASURES:ThetimeanddistanceofratsswimmingintheMorriswatermaze;thelatenttimeandtimesofmistakeinstep-throughtest;thebioactivityofCholineacetyltransferase(ChAT)inhippocampus;thenumberandsurfaceofGlialderivedneurotrophicfactor(GDNF)cellsintheCA4partofhippocampus.RESULTS:ThetimeanddistanceoftheratswithHDweresignificantlylongerinMorriswatermaze.Theswimmingtimeoftheratsinlowdoseandmiddledoseofshenwucapsulegroupswas24.01%and32.64%shorterrespectivelythanthatofthe3-PNAgroup.Instep-throughtests,theratsin3-NPAgroupshowedashorterlatenttimethanthatoftheratsinthecontrolgroupbeforeenteringthedarkchamber.Thelatenttimeinhigh-doseofandmiddle-doseshenwucapsulegroupswaslongerthantha
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