盐酸多奈哌齐对拟VD大鼠模型海马神经元保护作用机制的研究  

Studies on the mechanism of Donepezil' s protection in neuron of Hippocampus in mice with Vascular Dementia

作　　者：樊素琴[1] 刘合玉[1] 杨伟民[1] 邢陆伟[2] 闫丙川 

机构地区：[1]郑州大学第二附属医院神经康复科,450014 [2]郑州大学基础医学院机能实验中心,450052 [3]漯河市人民医院神经内科,462000

出　　处：《中国老年保健医学》2006年第2期25-30,共6页Chinese Journal of Geriatric Care

摘　　要：目的观察盐酸多奈哌齐对血管性痴呆(VD)大鼠模型海马NMDA受体亚单位NPR1的免疫组织化学表达的变化,及对GSH-PX、CAT的影响,探讨其在血管性痴呆中的神经保护作用机制。方法采用双侧颈总动脉反复夹闭、再通, 并腹腔注射硝普钠法制备模型,药物组用盐酸多奈哌齐溶液灌胃;用Y-型迷宫试验观察其行为学改变;用免疫组织化学技术观测大鼠海马神经元N-甲基-D -天门冬氨酸受体-R1的表达变化;GSH-PX、CAT分别采用DTNB法及紫外分光光度法测定其活力。结果盐酸多奈哌齐组大鼠学习、记忆成绩优于模型组 (P<0．01),其海马CA1区NMDA受体-R1表达明显降低,与模型组比较有显著性差异(P<0．01);GSH-PX、CAT较模型组明显增高(P<0．01),与假手术组相比无显著性差异(P>0．05)。结论盐酸多奈哌齐可通过降低NMDAR1的表达,提高GSH-以、CAT的活力来保护VD大鼠海马神经元。Objective To observe the effects of Donepezil on expression of N -methyl - D - aspartate receptor subunit proteins NR1 and influence of it on GSH - PX. CAT in neuron of Hippocampus in mice with Vascular Dementia, and probe the mechanism of Donepezil, s neuroprotection. Methods The mice were subjected for reperfusion repeatedly on bio - lateral common carotid arteries by repeatedly clipping and injected sodium nitroprusside into the abdominal cavity to establish the imitative vascular dementia rat models. Donepezil was given to the mice in medication group, The behavioral abnormalities were investigated by Y - type maze test; the expressions of N - methyl - D - aspartate receptor subunit proteins NR1 in neuron of hippocampus were observed by immunohistochemistry technique; and the activity of GSH - PX and CAT were measured with DTNB and UV methods respectively. Results Compared with model group, the performance records of learning and memory in Donepezil group were better (all P < 0.01) , the activity of GSH - PX and CAT were increase clearly (P< 0.01), there was no obvious difference of the results between Donepezil group and sham - operated group( P > 0.05), but the expression of N -methyl - D - aspartate receptor subunit proteins NR1 were decreased evidendy( P < 0.01), there was clear difference of the results between Donepezil group and model group but no difference with sham - operated group. Conclusions Low expression of N - methyl - D -aspartate receptor subunit proteins NR1 and high activity of GSH - PX and CAT may be involved in mechanism of Donepezil,s neuroprotective action.

关 键 词：血管性痴呆 N-甲基-D-天门冬氨酸受体亚单位NR1 盐酸多奈哌齐 GSH-PX CAT 海马神经元 

分 类 号：R749.2[医药卫生—神经病学与精神病学]