盐酸多奈哌齐对血管性痴呆小鼠海马ERK2及p-ERK表达变化的影响  

The effect of donepezil hydrochloride on the changes of ERK2 and p-ERK in hippocampus of mice with vascular dementia

作　　者：王雪笠[1] 胡亚卓[1] 吕佩源[1] 肖向建[1] 董艳红[1] 翟金萍[2] 何春年[2] 

机构地区：[1]河北医科大学神经内科教研室,河北石家庄050017 [2]河北省人民医院

出　　处：《中国老年学杂志》2008年第5期426-428,共3页Chinese Journal of Gerontology

基　　金：国家人事部2001年度留学人员科技活动择优资助项目(人发2001-119-1)

摘　　要：目的探讨盐酸多奈哌齐对血管性痴呆(VD)小鼠海马中细胞外信号调节激酶(ERK2、p-ERK)表达变化的影响。方法采用双侧颈总动脉反复缺血-再灌注法制备小鼠VD模型。将小鼠随机分为对照组、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ERK2及海马CA3区p-ERK的表达变化。结果盐酸多奈哌齐明显改善了VD小鼠学习、记忆成绩(P<0.05)。模型组海马CA1区ERK2的阳性细胞数目较对照组,药物组减少(P<0.05),阳性细胞平均光密度值亦较对照组、药物组降低(P<0.05);CA3区p-ERK阳性部位平均光密度值较对照组、药物组降低(P<0.05)。而药物组与对照组间上述变化无显著性差异(P>0.05)。结论ERK2的表达减少可能参与了VD的发病机制,盐酸多奈哌齐通过增加乙酰胆碱含量,后者作用于毒蕈碱乙酰胆碱受体(M受体)激活ERK(p-ERK),有助于改善学习和记忆功能。Objective To observe the effect of donepezil hydroehloride on the changes of extracellular signal-regulated kinase （ ERK2 and p-ERK） in hippocampus of mice with vascular dementia （VD）. Methods Kunming mice were divided into sham, model 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 behavioral scores of three groups were investigated by step-down test and water maze test at days 29, 30 respectively. The expressing changes of ERK2 in hippoeampus CA1 and p-ERK in hippoeampus CA3 were observed by immunohistochemistry technique. Results The grades of learning and memory of VD mice were obviously improved by donepezil hydrochloride （ P 〈 0. 05 ）. The number of positive ERK1 neurons [ （ 16. 17±0. 75） vs （23.17 ±1.08） , P 〈0.05] was less, the average optical of positive neurons was also lower [ （0. 208 3±0. 004 8） vs （0. 240 0 ±0. 005 8） , P〈0. 05] in hippoeampus CA1 of model group than that in sham group. The average optical of positive p-ERK in hippocampus CA3 was lower than that in sham group [ （0. 186 7 ±0. 008 4） vs （0. 271 7 ±0. 012 2） ; P 〈 0. 05 ]. However, there was no significant difference between sham and treatment group （ P 〉 0. 05 ）. Conclusions The decreased expression of ERK2 and p-ERK in hippecampal neurons may participate in the pathogenesis of VD. Donepezil hydroehloride could increase the content of acetylcholine 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：R743[医药卫生—神经病学与精神病学]