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

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.

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

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.