蛇床子素减轻Aβ_(25-35)诱导的大鼠学习记忆减退及海马神经元结构损伤  

Osthole attenuates learning and memory deficits and neuronal ultrastructure in CA1 region of hippocampus induced by Abeta 25-35 fragment in rats

作　　者：龚其海[1] 石京山[1] 杨丹莉[1] 

机构地区：[1]遵义医学院药理学教研室,贵州遵义563000

出　　处：《遵义医学院学报》2011年第4期335-337,340,共4页Journal of Zunyi Medical University

基　　金：贵州省教育厅自然科学基金项目[黔科教(2009)0111]

摘　　要：目的观察蛇床子素对-淀粉样蛋白25-35片段(Aβ25-35)诱导的大鼠学习记忆减退及海马神经元结构损伤的影响。方法 40只雄性SD大鼠随机均分为假手术组、模型组、阳性药组及蛇床子素组,阳性药组每日1次灌胃多奈哌齐1 mg/kg,蛇床子素组每日1次灌胃蛇床子素40 mg/kg,连续17 d,假手术组、模型组灌胃等体积的生理盐水,3 d后右侧脑室注射Aβ25-35制模,制模后d 10开始Morris水迷宫检测大鼠的空间记忆能力,透射电镜观察大鼠海马CA1区神经元结构损伤。结果右侧脑室注射Aβ25-35后,大鼠在定向航行实验中的逃避潜伏期明显增加(<0.01),空间探索实验中的校正逃避潜伏期缩短(<0.01),海马CA1区神经元结构明显受损;然而,蛇床子素及多奈哌齐明显缩短了大鼠的定向航行实验中的逃避潜伏期(<0.01),延长了空间探索实验中的校正逃避潜伏期(<0.01),减轻了海马CA1区神经元结构损伤。结论蛇床子素可减轻Aβ25-35诱导的大鼠学习记忆减退及海马神经元结构损伤。Objective To investigate the protective effect of osthole on learning and memory deficits and neuronal ultrastructure in CA1 region of hippocampus induced by Abeta 25-35 fragment（Aβ25-35）in rats.Methods Forty male Sprague Dawley rats were randomly divided equally into sham,model,positive-and osthole-treated groups.Positive-treated groups were administrated with donepezil at doses of 1.0 mg/kg once daily by gavage consecutive for 17d,osthole-treated groups were administrated with osthole at doses of 40 mg/kg,while sham and model groups were administrated with volume-matched normal saline by gavage,instead.After having treated for 3d,rat model with learning and memory deficits and neuronal ultrastructure was induced by injection of Aβ25-35 to lateral cerebral ventricle.And 10 d later after model establishment,the ability of learning and memory of rats was tested by Morris water maze,neuronal ultrastructure in CA1 region of hippocampus was observed by transmission electron microscopy.Results Injection of Aβ25-35 to lateral cerebral ventricle significantly increased eseape latencey in the place navigation test,and decreased adjusted eseape latencey in spatial probe test（P0.01）.Meanwhile,Aβ25-35 injection caused neuronal ultrastructure injury in CA1 region of hippocampus.However,treatments with donepezil or osthole significantly shortened eseape latency in the place navigation test,and increased adjusted eseape latency in spatial probe test,and attenuated neuronal ultrastructure injury in hippocampus.Conclusion Osthole may attenuate spatial learning and memory deficits and neuronal ultrastructure injury induced by Aβ25-35 in rats.

关 键 词：蛇床子素 淀粉样蛋白 学习 记忆 神经元 大鼠 

分 类 号：R971[医药卫生—药品]