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作 者:尹龙[1] 田金洲[1] 时晶[1] 王蓬文[2] 孔明望[1] 曾垂友[1] 任映[2]
机构地区:[1]北京中医药大学东直门医院老年病科,北京100700 [2]北京中医药大学东直门医院中药药理实验室,北京100700
出 处:《中华中医药杂志》2011年第8期1822-1825,共4页China Journal of Traditional Chinese Medicine and Pharmacy
基 金:高等学校学科创新引智计划(No.B08006);国家自然科学基金(No.30973738)~~
摘 要:目的:通过观察金思维对APPV717I转基因小鼠早期空间学习记忆能力及突触蛋白表达水平的影响,揭示其可能的作用机制。方法:将3月龄APPV717I转基因小鼠60只随机分为模型组、多奈哌齐组(0.00092g.kg-1.d-1)、金思维小(0.075g.kg-1.d-1)、中(0.15g.kg-1.d-1)和大剂量组(0.3g.kg-1.d-1),每组12只;同月龄遗传背景相同的C57BL/6J小鼠12只作为正常组,灌胃给药(0.01mL/g体质量),每日1次。在给药4个月后(7月龄)以Morris水迷宫进行行为学检测,以免疫组化的方法测定海马CA1区突触蛋白CaMKⅡ的表达水平。结果:行为学实验结果表明,与模型组比较,GEPT各剂量组能不同程度改善APPV717I转基因小鼠的空间学习记忆能力(P<0.05),免疫组化结果显示GEPT小剂量组CaMKⅡ平均光密度与模型组比较明显增加(P<0.05)。结论:GEPT可能通过提高突触相关蛋白CaMKⅡ在海马CA1区的表达从而改善APPV717I转基因小鼠早期的学习记忆能力。Objective:To investigate the effect of GEPT on spatial learning ability of the APPV717I transgenic mice at the early stage of dementia and its possible mechanism.Method:sixty three months old APPV717I transgenic mice were randomly divided into three GEPT groups by intragastric administration at doses of 0.075,0.15,0.3g·kg-1·d-1,a donepezil group by intragastric administration of 0.00092mg·kg-1·d-1,and an APPV717I transgenic model group,twelve C57BL/6J were set as a normal group by intragastric administration of distilled water.Four months later,Spatial learning ability was measured in Morris water maze.The expression level of CaMKⅡ in CA1 subfield within the hippocampus was determined using immunohistochemical stains and Image-Pro plus analysis.Result:After a four-month treatment of GEPT,the mean escape latency were significantly shortened(P0.05),and the target quadrant searchtime were significantly increased(P0.05) compared to the APPV717I transgenic model mice.There was a significant higher level in the expression of CaMKⅡ associated with the average optical density in the hippocampal CA1 area of the APPV717I transgenic mice treated with low dose of GEPT than that of the APPV717I transgenic model mice.Conclusion:the mechanism of GEPT's improving the spatial memory ability of APPV717I transgenic mice at an early stage of dementia may be enhancing the expression of CaMKⅡin the hippocampus.
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