盐酸多奈哌齐对血管性痴呆小鼠学习记忆及海马ERK1、p-ERK表达变化的影响  

The effect of donepezil hydrochloride on learning and memory and the changes about ERK1 and p-ERK in hippocampus of mice with vascular dementia

作　　者：胡亚卓[1] 昌佩源[1] 靳玮[1] 梁翠萍[1] 翟金萍[2] 何春年[2] 

机构地区：[1]河北省人民医院神经内科,石家庄050051 [2]河北省人民医院病理科,石家庄050051

出　　处：《中国行为医学科学》2008年第2期103-105,共3页Chinese Journal of Behavioral Medical Science

基　　金：国家人事部2001年度留学人员科技活动择优资助项目（2001-119-1）;河北省自然科学基金资助项目（301415）

摘　　要：目的探讨盐酸多奈哌齐对血管性痴呆（VD）小鼠学习记忆及海马中细胞外信号调节激酶（ERK1、p-ERK）表达变化的影响。方法采用双侧颈总动脉反复缺血一再灌注法制备小鼠VD模型。将小鼠随机分为假手术组、模型组及药物组，药物组给予盐酸多奈哌齐灌胃治疗。术后第29，30天，经跳台试验和水迷宫试验对各组小鼠进行行为学成绩测试，用免疫组化方法观察各组小鼠海马CA1区ERK1及海马CA3区p-ERK的表达变化。结果盐酸多奈哌齐显著改善了VD小鼠学习、记忆成绩[（34．90±9．56）sVS（62．81±10．70）s；（158．20±26．57）sVS（92．81±19．44）s；（76．65±9．46）sVS（122．15±11．96）s；（98．55±6．45）sVS（127．69±8．84）s；P〈0．05]。同时，模型组海马CA1区ERK1的阳性细胞数较假手术组减少[（16．50-1-1．95）VS（22．67±1．12）；尸〈0．05]、阳性细胞平均光密度值亦较假手术组降低[（0．2111±0．0049）VS（0．2700±0．0066）；P〈0．05]；CA3区p-ERK阳性部位平均光密度值较假手术组降低[（0．1867±0．0084）V8（0．2717±0．0122）；P〈0．05]。而治疗组与假手术组间上述指标差异无显著性（P〉0．05）。结论盐酸多奈哌齐通过抑制乙酰胆碱酯酶的活性，从而增加大脑乙酰胆碱含量，后者作用于M乙酰胆碱受体激活ERK。有助于改善学习和记忆功能。Objective To observe the effect of donepezil hydrochloride on learning and memory and the changes about extracellular signal-regulated kinase （ERK1 and p-ERK） in hippocampus of mice with vascular dementia（VD）. Methods Kunming mice were divided into sham group, model group and treatment group with donepezil hydrochloride randomly. The models of VD mice were established through three times ischemia-reperfusion of bilateral common carotid arteries. The mice from drug group were treated with donepezil hydrochloride. The behavioral scores of three groups were investigated by step-down test and water maze test at days 29, 30 respectively. The expressing changes of ERK1 in hippocampus CA1 and p-ERK in hippocampus CA3 were observed by immunohistochemistry technique. Results The grades of learning and memory of VD mice were obviously improved by donepezil hydrochloride [ （34.90 ± 9.56） vs （62.81 ± 10.70） ; （ 158.20 ± 26.57 ） vs （ 92.81 ± 19.44 ） ; （76.65 ± 9.46） vs （ 122.15 ± 11.96） ; （98.55 ± 6.45 ） vs （ 127.69 ± 8.84） ; P 〈 0.05 ]. The number of positive ERK1 neurons in hippocampus CA1 of model group was less than sham group [ （ 16.50 ± 1.95） vs （22.67 ± 1.12） ; P 〈 0.05 ], and the average optical of positive neurons was also lower [ （0.2111 ± 0.0049） vs （0.2700 ±0. 0066） ; P〈0.05 ]. The average optical of positive p-ERK in hippocampus CA3 was lower than sham group [ （0. 1867 ±0.0084） vs （0.2717 ±0. 0122） ; P 〈 0.05 ]. However, there was no significant difference between sham group and treatment group （ P 〉 0.05）. Conclusion The decreased expression of ERK1 and p-ERK in hippocampal neurons might participate the pathogenesis of vascular dementia. Donepezil hydrochloride could increase the content of acetylcholine by inhibiting the activities of acetylcholinesterase, which could activate ERK through M receptor and furthermore improve abilities of learning and memory.

关 键 词：血管性痴呆 小鼠 细胞外信号调节激酶 免疫组化 海马 

分 类 号：R749.1[医药卫生—神经病学与精神病学]