盐酸多奈哌齐对血管性痴呆小鼠海马神经细胞神经元蛋白激酶C表达变化的影响

目的探讨盐酸多奈哌齐对血管性痴呆（Vascular dementia,VD）小鼠海马神经元蛋白激酶C（protein kinase C,PKC）变化的影响。方法将3月龄雄性昆明小鼠随机分为假手术组、模型组、多奈哌齐治疗组。采用双侧颈总动脉结扎,反复缺血-再灌注制备VD模型,药物治疗30d。术后第29、30天,分别进行跳台试验和水迷宫试验观察各组小鼠行为学改变。采用免疫组织化学法观察各组海马CA1区神经元PKC表达的变化。结果药物治疗组小鼠学习、记忆成绩较模型组明显改善（P〈0.05）。模型组PKC免疫反应阳性神经元平均光密度值为（0.2730±0.0709）,与假手术组（0.3206±0.0642）和药物组（0.3036±0.0688）相比均显著降低（P〈0.05）,而药物组与假手术组间无明显差别（P〉0.05）。结论反复缺血-再灌注导致VD小鼠海马神经元PKC表达减少;多奈哌齐通过抑制中枢神经系统中乙酰胆碱的降解,可增加VD小鼠海马神经元PKC表达,从而改善VD小鼠学习、记忆能力,推测此也是该药物改善VD小鼠学习、记忆障碍的一个重要环节。

Effects of donepezil hydrochloride on the protein kinase C expression changes in hippocampal neuron of mice with vascular dementia

Objective To explore the effects of Donepezil Hydrochloride on the protein kinase C （PKC） expression changes in hippocampal neurons of mice with vascular dementia （VD）. Methods 3 months old Kunming mice were divided into sham group, model group and Donepezil Hydrochloride treatment group randomly. The model of VD mice was established through three times ischemia—reperfusion of bilateral common carotid arteries. The drug group mice were treated with Donepezil Hydrochloride for 30 days. The behavioral scores in all mice were investigated by step-down test and water maze test at days 29, 30, respectively. PKC expression in hippocampus CA1 was observed by immunohistochemistry. Results The grades of learning and memory of treated mice were obviously improved by Donepezil Hydrochloride （P 〈 0.05）. The PKC expression in model group hippocampus CA1 was significantly lower than in the sham group （P 〈 0.05） and the drug group （P 〈 0.05）. Conclusions Reiterative ischemia—reperfusion of bilateral common carotid arteries can result in the decreased expression of PKC in hippocampus neurons of VD, which could be ameliorated by Donepezil Hydrochloride through inhibiting the breaking down of acetylcholine. It might be an important element for Donepezil Hydrochloride to improve the abilities of learning and memory of VD.