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作 者:丁月霞[1,2] 张丽[1] 叶翠飞[1] 王文[1] 李林[1]
机构地区:[1]首都医科大学宣武医院药物研究室,神经变性病教育部重点实验室,北京100053 [2]烟台毓璜顶医院药学部,烟台264000
出 处:《中国新药杂志》2010年第2期133-138,共6页Chinese Journal of New Drugs
基 金:国家重点基础发展计划973计划(2003CB517104);国家自然科学基金(90709011);北京市自然科学基金项目(7050001,7062051);北京市科技计划项目(D0206001043191)
摘 要:目的:探讨山茱萸环烯醚萜苷(cornel iridoid glycoside,CIG)对脑损伤大鼠模型学习记忆能力的影响及其作用机制。方法:采用穹隆海马伞切断(Fimbria-fornixtransaction,FFT)制备机械性脑损伤大鼠模型。造模后灌胃给予CIG(20,60和180 mg.kg-1)21 d,应用避暗试验和Morris水迷宫试验测定大鼠学习记忆能力的变化。然后立即取脑,采用免疫组织化学染色法和Western blot法测定脑海马区突触生长素(syn-aptophysin,SYP)表达的变化。结果:在避暗试验中,FFT模型大鼠潜伏期较假手术对照组明显缩短(P<0.01),CIG(60和180 mg.kg-1)组与模型组相比潜伏期显著延长(P<0.05)。在Morris水迷宫试验中,模型大鼠逃避潜伏期与假手术对照组相比明显延长(P<0.01),CIG(20和60 mg.kg-1)灌胃给药可显著缩短模型大鼠的逃避潜伏期(P<0.05,P<0.01)。免疫组织化学和Western blot检测结果显示,模型组大鼠海马区SYP表达比假手术对照组明显减少(P<0.01);CIG(20,60和180 mg.kg-1)可显著增高模型大鼠脑海马区SYP的表达水平(P<0.05,P<0.01)。结论:CIG灌胃给药能够提高FFT模型大鼠的学习记忆能力,推测其机制之一可能与CIG增强海马区SYP的表达、从而促进突触重建有关。Objective: To investigate the effect of cornel iridoid glycoside(CIG) on learning-memory ability and its mechanisms in rats with brain injury. Methods: Mechanical brain injury was induced by fimbria-fornix transaction(FFT) in rats. After the operation, rats were administered by intragastric CIG (20, 60 and 180 mg· kg^-1) for 21 days. The learning and memory abilities were determined by the step-through test and Morris water maze test. Then the brain was immediately removed, and the expression of hippocampal synaptophysin(SYP) was detected by immunohistoehemistry and Western blotting. Results: In the step-through test, the FFT rats showed shorter latency as compared with the sham-operated rats( P 〈 0.0l ). Intragastrie CIG ( 60 and 180 mg· kg^-1 ) significantly prolonged the latency of FFT rats(P 〈0.05) rats was significantly longer than that in sham-operated In the Morris water maze test, the escape latency in FFT rats(P 〈0.01), and CIG(20 and 60 mg· kg^-1) obviously rats(P 〈0.05, P 〈 0.01 ). Conclusion: Intragastric administration of CIG markedly improved learning-memory ability in FFT rats, and one of the mechanisms may be related to elevating hippocampal SYP expression and thus promoting synapses restitution.
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