盐酸多奈哌齐对阿尔茨海默病大鼠脑内NOS、AchE蛋白表达的影响

Impact of Donepezil Hydrochloride on Protein Expressions of Nitric Oxide Synthase And Acetylcho -linesterase in a Rat Brain Model of Alzheimer＆#39;S Disease

【目的】探讨盐酸多奈哌齐对阿尔茨海默病（AD）模型大鼠脑组织中一氧化氮合酶（NOS）、乙酰胆碱酯酶（AchE）蛋白表达的影响。【方法】将40只 SD 大鼠随机分成正常组、假手术组、模型及治疗组，每组10只 。 用 β淀粉样蛋白1‐40（ Aβ1‐40）制备 AD 大鼠模型，造模2周后治疗组给予盐酸多奈哌齐灌胃。评价大鼠的学习记忆功能（逃避潜伏期），给药28 d 后免疫组化法观察各组大鼠脑组织中 NOS 、AchE 的表达情况。【结果】给药前模型组和治疗组大鼠逃避潜伏期明显延长，与正常组和假手术组比较有统计学差异（ P ＜0．01）；给药后治疗组逃避潜伏期较模型组明显缩短（ P ＜0．05）。各组 NOS 、AchE 的阳性表达主要区域在海马，正常组和假手术组 NOS 、AchE 的阳性表达比较无显著性差异（ P ＞0．05），但均高于模型组和治疗组（ P ＜0．05）。治疗组脑内 NOS 阳性表达较模型组显著增高，AchE 表达显著降低，差异有统计学意义（ P ＜0．05）。【结论】盐酸多奈哌齐能促进 AD大鼠学习记忆功能恢复，其作用机制除可明确抑制 AchE 活性外，还与增加海马神经元细胞 NOS 的蛋白表达有关。

[Objective] To observe the impact of donepezil hydrochloride on positive expressions of nitric oxide synthase （NOS） and acetylcholinesterase （AchE） in brain tissue of a rat model of Alzheimer＇s disease （AD ） .[Methods] A total of 40 Sprague‐Dawley rats were randomly divided into normal ,sham operation ,model and treatment groups （ n = 10 each） .The AD rat model was induced with amyloid beta peptide 1‐40 （Aβ1‐40） .After 2 weeks ,the treatment group received oral donepezil hydrochloride .For evaluating cognitive functions ,the posi‐tive expressions of NOS and AchE were detected by immunohistochemistry in brain tissues at Day 28 post‐dosing .[Results] After modeling ,escape latency became obviously longer （ P 〈 0 .01） .And significant statistical differ‐ence existed between treatment and model groups after dosing （ P 〈 0 .05） .The positive expressions of NOS and AchE were detected in hippocampal brain tissues .NOS expression decreased and AchE increased in brain tissues of model group compared with normal and sham operation groups .And the differences were statistically significant （ P 〈 0 .01） .Compared with model group ,NOS expression increased and AchE decreased in treatment group . And the difference was statistically significant （ P 〈 0 .01） .[Conclusion] Donepezil hydrochloride can promote cog‐nitive functions of AD rats .The effect may be mediated though specifically inhibiting the activity of AchE and an up‐regulation of NOS protein expression in hippocampal neuron cells .