盐酸多奈哌齐对血管性痴呆模型小鼠海马神经元ERK表达的影响

目的探讨盐酸多奈哌齐对血管性痴呆(VD)模型小鼠海马神经元中细胞外信号调节激酶(ERK)表达的影响。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。将小鼠随机分为假手术组、模型组及盐酸多奈哌齐治疗组,药物组给予盐酸多奈哌齐灌胃治疗。术后第29、30天,采用跳台试验和水迷宫试验对各组小鼠进行行为学成绩测试,采用免疫组化法观察各组小鼠海马神经元ERK表达的变化。结果盐酸多奈哌齐可明显改善VD模型小鼠学习、记忆成绩(P<0.05)。模型组小鼠海马CA1区ERK1、ERK2表达及海马CA3区p-ERK表达较假手术组及治疗组减少(均P<0.05)。结论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,从而有助于改善学习和记忆功能。海马神经元内ERK的表达减少可能参与了VD的发病机制。

Effect of Donepezil Hydrochloride on the Changes about ERK in the Hippocampal Neurons of Mice with Vascular Dementia

Objective To observe the effect of donepezil hydrochloride on the changes about extracellular signal-regulated kinase(ERK) in the hippocampal neurons of mice with vascular dementia(VD).Methods Kunming mice were divided into the sham operated 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 ERK in hippocampal neurons were observed by immunohistochemical technique.Results The grades of learning and memory of VD mice were obviously improved by donepezil hydrochloride(P<0.05).The expression of ERK1,ERK2 in the hippocampus CA1 and p-ERK in hippocampus CA3 was significantly lower in the model group than that in the sham operated group(P<0.05) and the drug group(P<0.05).Conclusions The decreased expression of ERK in the hippocampal neurons might participate the pathogenesis of VD.Donepezil hydrochloride could increase the content of acetylcholine which could activated ERK through M-receptor and furthermore improved abilities of learning and memory.