氟马西尼和纳洛酮对东莨菪碱致大鼠认知功能障碍的影响  

Effects of flumazenil and naloxone on scopolamine-induced impairment of spatial working memory in rats

作　　者：谈大海[1] 张焰[2] 陈正[2] 

机构地区：[1]徐州医学院江苏省麻醉学重点实验室,221002 [2]苏州大学附属第四医院麻醉科

出　　处：《中华麻醉学杂志》2010年第3期320-323,共4页Chinese Journal of Anesthesiology

摘　　要：目的 探讨氟马西尼和纳洛酮对东莨菪碱致大鼠认知功能障碍的影响.方法 健康清洁级雄性SD大鼠40只,随机分为4组（n=10）：正常对照组（C组）腹腔注射等容量生理盐水;东莨菪碱组（S组）腹腔注射东莨菪碱0.8 mg/kg;东莨菪碱＋氟马西尼组（SF组）腹腔注射东莨菪碱0.8 mg/kg和氟马西尼0.5 mg/kg;东莨菪碱＋纳洛酮组（SN组）腹腔注射东莨菪碱0.8 mg/kg和纳洛酮2 mg/kg.1次/d,连续3 d.于第3天末次给药后30 min采用Y型迷宫进行学习记忆能力测试,记录达标训练次数和达标时间.处死后取脑,冰浴下分离海马,应用免疫组化法计数胆碱乙酰基转移酶（ChAT）免疫阳性神经元,采用RT-PCR法测定毒蕈碱受体M1亚型（mAChRM1）mRNA的表达.结果 与C组比较,S组、SF组和SN组达标时间延长,训练次数增加,ChAT阳性神经元计数减少,mAChRM1 mRNA表达下调（P〈0.05）.与S组比较,SF组和SN组达标时间缩短,训练次数减少,ChAT阳性神经元计数增多,mAChRM1 mRNA表达上调（P〈0.05）.结论 氟马西尼和纳洛酮可减轻东莨菪碱致大鼠认知功能障碍,其机制可能与改善大鼠中枢胆碱能神经系统功能有关.Objective To investigate the effects of flumazenil and naloxone on scopolamine-induced impairment of spatial working memory in rats.Methods Forty pathogen-free SD rats weighing 160-200 g were randomly divided into 4 groups（n=10 each）：group I control（group C）;group IIscopolamine（group S）;group III flumazenil＋scopolamine（group SF）and group IV naloxone＋scopolamine（group SN）.Scopolamine 0.8 mg/kg was administered IP once a day for 3 consecutive days in group II-IV.In group SF and SN flumazenil 0.5 mg/kg and naloxone 2 mg/kg were administered IP respectively once a day for 3 consecutive days in addition to scopolamine.Thirty minutes after last IP administration,cognitive function was assessed using Y-maze.The animals were killed after cognitive function assessment and bilateral hippocampi Were isolated for determination of mAChRM1 mRNA expression（by RT-PCR）and detection of ChAT positive neurons（by immuno-histochemistry）.Results Cognitive dysfunction developed in group S as compared with control group and was ameliorated in group SF and SN.The number of ChAT positive neurong and mAChRM1 mRNA expression were significantly decreased in group S compared with control group and were significantly higher in group SF and SN than in group S.Conclusion Flumazenll and naloxone can ameliorate the scopolamine-induced impairment of spatial working memory by improving cholinergic neuron function.

关 键 词：氟马西尼 纳洛酮 东莨菪碱 海马 认知障碍 

分 类 号：R96[医药卫生—药理学]