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作 者:王佳[1] 杨晓云[1,3] 唐庆娟[2] 王玉明[2] 王金红[1] 曲梅花[1]
机构地区:[1]潍坊医学院山东省高校应用药理学重点实验室,潍坊医学院药理学教研室,山东潍坊261053 [2]中国海洋大学食品科学与工程学院,山东青岛266003 [3]潍坊医学院生物化学与分子生物学教研室,山东潍坊261053
出 处:《中国海洋药物》2016年第2期59-64,共6页Chinese Journal of Marine Drugs
基 金:“十二五”国家科技支撑计划项目(2012BAD33B07);国家自然科学基金项目(31071525;31101281;81170974);山东省自然基金项目(ZR2009CL047);山东省教育厅基金项目(J14LK15)资助
摘 要:目的研究二十二碳六烯酸-磷脂(docosahexaenoic acid-phosphatidylcholine,DHA-PC)对海马CA1区注射Aβ25-35所致的阿尔茨海默病(Alzheimer’s disease,AD)大鼠模型学习记忆能力改善作用,为DHA-PC的药用开发奠定理论基础。方法 SPF级雄性Wistar大鼠40只,250~300g,随机分为正常对照组、AD组、多奈哌齐组、DHA-PC组。大鼠双侧海马CA1区注射Aβ25-35制作AD大鼠模型,水迷宫检测学习记忆能力改变,检测Tau(Ser 396)蛋白的含量,检测超氧化物歧化酶活性。结果水迷宫结果显示:与AD组相比,定向航行实验DHA-PC组大鼠的潜伏期明显降低(P〈0.05);空间探索实验DHA-PC组大鼠在安全平台所在象限的活动时间明显增加(P〈0.05)。与AD组相比,DHA-PC组和DHCI组大鼠皮层和海马的Tau(Ser396)蛋白含量明显降低(P〈0.05,P〈0.01),DHA-PC组和DHCI组皮层SOD活性增强(P〈0.01)。结论 DHA-PC可通过降低皮层和海马396位点磷酸化Tau蛋白的表达和增强SOD活性,改善AD大鼠学习记忆能力,具有较好的药用开发前景。Objective To investigate the effect and molecular mechanism of docosahexaenoic acid-phosphatidylcholine(DHA-PC)on the cognitive deficits of Alzheimer disease(AD)rats induced by Aβ25-35.Methods Fourty male Wistar rats(BW 250-300g)were randomly divided into control group,AD group,donepezil group and DHA-PC group.Aβ25-35 was injected into hippocampus CA1 area of the AD group rats and drug treatment group rats.All the groups were tested with Morris water maze after administration.DHA-PC 200 mg·kg-1 30 days in rat hippocampus and cerebral cortex the phosphorylated Tauprotein of Ser396 site was determined with western blot and the activity of superoxide dismutase(SOD)was also determined.Results In the results the latency period of the DHA-PC group was significant decreased compared with the AD group(P〈0.05).In the probe trial,the DHA-PC group spent more time in the target area compared with AD group(P〈0.05).The results of western blot were shown that DHA-PC and donepezil treatment reduced the phosphorylated tau protein of Ser396 site expression in cortex and hippocampus(P〈0.05,P〈0.01).SOD activity in cortex was increased more significanthy in DHA-PC and donepezil treated groups than that in AD groups(P〈0.01).Conclusion DHA-PC teratment could improve the cognitive deficits in AD rats.
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