盐酸多奈哌齐对血管性痴呆小鼠学习和记忆能力的影响

目的观察盐酸多奈哌齐对脑缺血-再灌注后血管性痴呆小鼠不同时间点学习、记忆能力和海马CA1区病理变化的影响。方法雄性昆明小鼠250只,采用双侧颈总动脉反复缺血-再灌注的方法制备血管性痴呆(VD)模型,随机分为假手术组、模型组和多奈哌齐治疗组。应用Morris水迷宫实验、跳台实验进行行为学测试,HE染色观察海马病理表现及盐酸多奈哌齐对其的影响。结果术后4周时,模型组小鼠的学习、记忆成绩均明显劣于假手术组小鼠(P<0.05),病理改变较假手术组严重,这一变化持续至术后8周仍未恢复。盐酸多奈哌齐治疗组在术后4周和8周时,其学习、记忆能力和海马CA1区病理表现较模型组均有明显改善(P<0.05)。结论脑缺血-再灌注可导致小鼠海马CA1区神经元持续进行性损害,伴学习、记忆能力障碍;盐酸多奈哌齐对脑缺血-再灌注诱发的VD小鼠有一定治疗作用。

Effects of donepezil on the abilities of learning and memory in mice with vascular dementia

Objective To evaluate whether Donepezil hydrochloride have therapeutic effects on the learning and memory performance and neuronal pathology of hippocampus CA1 region at different time points after cerebral ischemiareperfusion in mice with vascular dementia （VD）. Methods Two hundreds and fifty male Kunming mice were randomly divided into three groups： the sham-operated group,the model group and the donepezil-treated group. VD mice were made by three times of transient ischemia-reperfusion of bilateral common carotid arteries with tail cut. The behavioral tests were done by Morris water maze and step-down probe. The neuronal pathological changes of the hippocampus were observed with HE staining . Results The learning and memory performances of model group were d.amaged significantly after 4 weeks and 8 weeks post surgery compared to sham-operated group （ P 〈 0.05 ）. The neuronal pathological injuries in model group were worsen than that in sham-operated group （ P 〈 0. 05 ）. Donepezil hydrochloride attenuated the behavioral and pathological deficits at 4weeks and 8 weeks post-surgery （P 〈 0.05 ）. ConcLusion Cerebral ischemia and reperfusion can induced severe memory deficits and neuronal degeneration in hippocampus in mice. Donepezil hydrochloride has treating effect on VD mice induced by cerebral ischemia and reperfusion.