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华中五味子酮对阿尔茨海默病样大鼠学习记忆功能及海马区核因子κB、诱导型一氧化氮合酶表达的影响
于方1,拓西平1*,吕建勇1,陈海生2
0
(1.第二军医大学长海医院老年病科,上海 200433;2.第二军医大学药学院药物化学教研室,上海 200438)
摘要:
目的:观察华中五味子酮(Schisandrone)对阿尔茨海默病(Alzheimer’s disease,AD)样大鼠学习记忆及海马区核因子κB(nuclear factor-κB)、诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)表达的影响,探讨华中五味子酮对AD可能的防治作用。方法:30只雄性SD大鼠随机分为空白对照组、AD模型组和华中五味子酮干预组3组,每组各10只。采用侧脑室立体定向注射β淀粉样蛋白(amyloid-beta protein, Aβ)25-35的方法,建立AD的动物模型;华中五味子酮干预组采用华中五味子酮灌胃进行药物干预,空白对照组注射生理盐水。通过Morris水迷宫检测大鼠学习、记忆能力,通过免疫组化法观察大鼠海马区NF-κB及iNOS 蛋白的表达。结果:华中五味子酮干预组大鼠短期学习记忆能力较AD样大鼠有明显改善(P<0. 05),海马区NF-κB及iNOS 的表达较AD样大鼠明显减少(P<0. 05),海马区NF-κB及iNOS 的表达呈正相关关系(空白对照组、AD模型组、华中五味子酮干预组的相关系数分别为0.639、0.656、0.682,P均<0. 05)。结论:华中五味子酮可能通过影响NF-κB信号转导通路而抑制Aβ诱导的氧化应激和炎性反应,在AD发病中具有保护作用。
关键词:  阿尔茨海默病  核因子κB  诱导型一氧化氮合酶  华中五味子酮  迷宫学习
DOI:10.3724/SP.J.1008.2007.01351
投稿时间:2007-05-11
基金项目:
Schisandrone improves learning and memory abilities of Alzheimer-like rats and influences expression of NF-κB, iNOS in rat hippocampus
YU Fang1,TUO Xi-ping1*,L Jian-yong1,CHEN Hai-sheng2
(1.Department of Geriatrics,Changhai Hospital,Second Military Medical University,Shanghai 200433,China;2.Department of Pharmacochemistry, School of Pharmacy, Second Military Medical University,Shanghai 200438)
Abstract:
Objective:To investigate the influence of Schisandrone on the learning and memory abilities of rats with Alzheimer-like disease and on the expression of NF-κB, iNOS in rat hippocampus, so as to study the prevention effect of Schisandrone on Alzheimer disease (AD). Methods: Totally 30 male SD rats were evenly randomized into 3 groups: blank control group, AD model group and Schisandrone intervention group. The AD animal model was established by stereotactic injection of Aβ25-35 into lateral cerebral ventricle of rats; the rats in Schisandrone intervention group were administrated with Schisandrone. The learning and memory abilities of animals were determined by Morris water maze; the expression of NF-κB, iNOS in the hippocampus was detected by immunohistochemistry. Results: The learning and memory abilities of rats in the Schisandrone intervention group were significantly improved compared with those in the AD model group (P<0.05). The expression of NF-κB and iNOS in the hippocampus was significantly decreased in the Schisandrone group than in the AD model group(P<0.05). The expression of NF-κB and iNOS in the hippocampus was positively correlated with each other. The correlation coefficients for the blank control,AD model and Schisandrone intervention groups were 0.639,0.656 and 0.682,respectively (all P<0. 05). Conclusion: Schisandrone can suppress the Aβ-induced oxidative stress and inflammatory reaction through influencing NF-κB signaling pathway, exerting its protective effect on AD.
Key words:  Alzheimer disease  nuclear factor-kappa B  inducible nitric oxide synthase  schisandrone  maze learning