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盐酸多奈哌齐治疗血管性痴呆的实验研究
引用本文:黄敬,梅元武,孙麓,俞善纯,高峻岭. 盐酸多奈哌齐治疗血管性痴呆的实验研究[J]. 华中科技大学学报(医学版), 2005, 34(6): 719-722
作者姓名:黄敬  梅元武  孙麓  俞善纯  高峻岭
作者单位:华中科技大学同济医学院附属协和医院神经内科,武汉,430022
基金项目:国家“十五”攻关基金资助项目(No.2001BA703B22)
摘    要:目的观察盐酸多奈哌齐对慢性局部脑血液低灌注大鼠(简称低灌注组)认知功能的改变并探讨其胆碱能机制。方法双侧颈总动脉结扎制模后的大鼠采用盐酸多奈哌齐连续治疗6周,再将其水迷宫试验、事件相关诱发电位(P300)、胆碱酯酶及胆碱纤维的测定结果与正常组、低灌注组及盐水治疗组相比较。结果低灌注组与正常组相比,水迷宫完成时间显著延长,错误次数显著增多,P300潜伏期显著延长,胆碱酯酶浓度及胆碱纤维密度也显著下降。盐酸多奈哌齐治疗组其胆碱酯酶浓度及胆碱纤维密度较低灌注组进一步下降,但水迷宫试验结果却较低灌注组显著好转,P300各波的潜伏期测定值也均显著优于低灌注组。结论慢性低灌注能显著影响大鼠的认知功能,盐酸多奈哌齐对慢性低灌注所造成的认知功能损害有肯定的防治作用,这一作用可能与抑制胆碱酯酶后脑组织中乙酰胆碱浓度升高有关。

关 键 词:脑缺血  痴呆  血管性  胆碱酯酶  盐酸多奈哌齐
修稿时间:2004-10-21

Experimental Study on the Treatment of Vascular Dementia with Aricept
Abstract:Objective To investigate the effect of aricept on cognition function of chronic cerebral hypoperfusion rats, and discuss its cholinergic mechanism.Methods The levels of cholinesterase and density of cholinergic fibres together with the results of experiments in water maze and the values of event related potentials (P300 latency) were recorded in normal group, chronic cerebral hypoperfusion group, control treatment group (physiological saline, 3.5 ml/kg every day for 6 weeks) and aricept treatment group (0.03 % aricept, 3 mg/kg every day for 6 weeks), respectively.Results The results of experiments in water maze and the values of P300 latency in chronic cerebral hypoperfusion group were worse than in normal group (P<0.05). A more significant decrease in cholinesterase levels and density of cholinergic fibres in cortex of frontal lobe and hippocampus zone was observed in chronic cerebral hypoperfusion group than in normal group (P<0.05). The results of experiments in water maze and the values of P300 latency in aricept treatment group were improved as compared with those in the chronic cerebral hypoperfusion group, but cholinesterase levels and density of cholinergic fibres in cortex of frontal lobe and hippocampus zone decreased severely as compared with those in chronic cerebral hypoperfusion group.Conclusion Chronic cerebral hypoperfusion can influence significantly the cognition function. Aricept may inhibit cholinesterase, thereby increasing acetylcholine, which has a positive effect on prevention and treatment of the injury of cognition function produced by chronic cerebral hypoperfusion.
Keywords:cerebral ischemia  dementia   vascular  cholinesterase  aricept
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