盐酸多奈哌齐对拟血管性痴呆大鼠海马神经元的保护机制  

Neuroprotective mechanism of Donepezil in hippocampus of mice with vascular dementia

作　　者：樊素琴[1] 刘合玉[1] 杨伟民[1] 邢陆伟[1] 闫丙川[1] 

机构地区：[1]郑州大学第二附属医院神经康复科,郑州第八人民医院三病区450014

出　　处：《临床神经病学杂志》2007年第6期441-443,共3页Journal of Clinical Neurology

摘　　要：目的探讨盐酸多奈哌齐对拟血管性痴呆(VD)大鼠海马神经元的保护机制。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VD模型后,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;用免疫组化技术检测大鼠海马神经元N-甲基-D-天门冬氨酸受体1(NR1)的表达;分别采用55二硫代二硝基苯甲酸(DTNB)法及紫外分光光度法测定其谷胱甘肽过氧化物酶(GSH-PX)、过氧化氢酶(CAT)活力,并与对照组比较。结果与VD对照组比较,盐酸多奈哌齐组大鼠学习、记忆成绩明显提高(均P<0.01);海马CA1区NR1表达明显降低(P<0.01);GSH-PX、CAT活性明显增高(均P<0.05)。结论盐酸多奈哌齐可能通过降低NR1的表达,提高GSH-PX、CAT的活力来保护VD大鼠海马神经元。Objective To probe the neuroprotective mechanism of Donepezil in hippocampus of mice with vascular dementia（VD）. 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 VD rat models. Then Donepezil was given by intragastric administration. 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 activities of glutathione peroxidase （GSH-PX） and catalase （CAT） were measured with dithio-bis-nitrobenzoic acid （DTNB） and ultraviolet spectrophotometry （UV） methods, respectively. Results Compared with VD control group, the performance records of learning and memory in Donepezil group were better （ all P 〈 0. 01 ） , the expression of NR1 was decreased evidently （P 〈 0. 01 ）, the activities of GSH-PX and CAT were increased clearly （ all P 〈 0. 05 ）. Conclusion Down-regulation expression of NR1 and up-regulation the activities of GSH-PX and CAT may be involved in the mechanisms of Donepezil＇s neuroprotective effect.

关 键 词：血管性痴呆 盐酸多奈哌齐 神经保护 

分 类 号：R749.1[医药卫生—神经病学与精神病学]