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目的观察盐酸多奈哌齐对于慢性低灌注大鼠额叶皮质及海马区胆碱酯酶浓度和胆碱酯酶阳性纤维密度的影响,并探讨其意义。方法雄性SD大鼠112只,分为正常组、模型组、盐水治疗组和盐酸多奈哌齐治疗组。后3组均行双侧颈总动脉结扎,盐酸多奈哌齐治疗组大鼠术后采用盐酸多奈哌齐灌胃,剂量为每日3mg/kg体重;盐水治疗组采用相同剂量的生理盐水灌胃,连续治疗6周后进行水迷宫实验,并测定各组大鼠的胆碱酯酶水平及胆碱酯酶阳性纤维密度。结果模型组大鼠与正常组大鼠相比,水迷宫完成时间显著延长,错误次数显著增多,胆碱酯酶浓度及胆碱酯酶阳性纤维密度也显著下降。盐酸多奈哌齐治疗组大鼠胆碱酯酶浓度及胆碱酯酶阳性纤维密度较模型组进一步下降,但水迷宫试验结果却较模型组大鼠有显著改善。结论慢性低灌注能显著影响大鼠的认知功能,其原因可能与低灌注大鼠胆碱能系统受损有关;盐酸多奈哌齐对慢性低灌注所造成的认知功能损害有一定的防治作用,这一作用可能与其抑制胆碱酯酶,从而使脑组织中乙酰胆碱浓度升高有关。
Objective To observe the effect of donepezil hydrochloride on cholinesterase and cholinesterase-positive fiber density in the frontal cortex and hippocampus in chronic hypoperfusion rats and to explore its significance. Methods One hundred and twelve male SD rats were divided into normal group, model group, saline treatment group and donepezil hydrochloride treatment group. The rats in the three groups were given ligation of the common carotid artery. The donepezil hydrochloride group was treated with donepezil hydrochloride intragastrically at a dose of 3 mg / kg body weight daily. The saline treatment group was given the same dose of saline for continuous treatment 6 Water maze test was performed after week, and cholinesterase level and cholinesterase-positive fiber density of rats in each group were determined. Results Compared with normal rats, the completion time of water maze was significantly prolonged and the number of mistakes significantly increased. The concentrations of cholinesterase and the density of cholinesterase positive fibers were also significantly decreased. The concentration of cholinesterase and the density of cholinesterase-positive fibers in the donepezil hydrochloride treatment group decreased further than those in the model group, but the water maze test results were significantly improved compared with the model group rats. Conclusion Chronic hypoperfusion can significantly affect the cognitive function of rats, which may be related to the impairment of cholinergic system in hypoperfusion rats. Donepezil hydrochloride may have a preventive and therapeutic effect on cognitive impairment induced by chronic hypoperfusion A role may be related to its inhibition of cholinesterase, so that the concentration of acetylcholine in brain tissue related.