《中国康复理论与实践》

《中国康复理论与实践》 ›› 2010, Vol. 16 ›› Issue (4): 311-313.

• 论文 • 上一篇    下一篇

霍乱毒素B亚单位-神经生长因子耦联制剂滴鼻对拟痴呆小鼠空间学习记忆的影响

张卿1,4，刘雁勇1，白丽敏2，石葛明3，万选才1，孙红梅2，左萍萍1   

  1. 1.中国医学科学院基础医学研究所；北京协和医学院基础学院药理室，北京市 100005；2.北京中医药大学解剖教研室，北京市 100029；3.河北医科大学神经生物学实验室，河北石家庄市 050017；4.中国科学院上海药物研究所药理一室，上海市 201203。
  • 收稿日期:2010-03-18 修回日期:1900-01-01 出版日期:2010-04-25 发布日期:2010-04-25
  • 通讯作者: 左萍萍

Effect of Nasal Administration of Compound of Cholera Toxin B Subunit and Nerve Growth Factor on Spatial Learning and Memory Abilities in the Amnesic Mice

ZHANG Qing, LIU Yan-yong, BAI Li-min, et al.   

  1. Departmemt of Pharmacology, Institute of Basic Medical Sciences, School of Basic medicine, PUMC & CAMS, Beijing 100005, China
  • Received:2010-03-18 Revised:1900-01-01 Published:2010-04-25 Online:2010-04-25

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被引次数

3

摘要： 目的观察霍乱毒素B亚单位(cholera toxin B subunit, CB)与神经生长因子(NGF)耦联制剂滴鼻治疗对拟痴呆小鼠学习记忆能力及胆碱能神经系统的影响。方法用改进的过碘酸钠法使CB-NGF耦联，滴鼻治疗脑室内注射β样淀粉蛋白(Aβ25-35)的拟AD小鼠模型；CB-NGF 7-5 μg/d、15 μg/d滴鼻治疗7 d，Morris水迷宫检测其空间学习记忆能力；免疫组织化学染色胆碱乙酰化酶(ChAT)。结果未经治疗的模型鼠寻台潜伏期明显延长(P<0-01)；在安全岛所在象限的停留时间明显缩短，斜角带区ChAT阳性细胞数量显著减少(P<0-001)。NGF及CB-NGF滴鼻治疗组寻台潜伏期有所缩短，在安全岛象限内的停留时间比模型组明显延长(P<0-01)；基底前脑斜角带区ChAT染色明显增多(P<0-01)。结论CB-NGF滴鼻治疗可改善痴呆小鼠的空间认知能力，与其保护胆碱能神经有关。

关键词: 霍乱毒素B亚单位, 神经生长因子, β样淀粉蛋白, Morris水迷宫, 胆碱乙酰转移酶

Abstract: ObjectiveTo explore the effects of the conjugate prepared from the cholera toxin B subunit(CB) and nerve growth factor(NGF) on the spatial learning and memory abilities and cholinergic function.MethodsThe conjugate of CB-NGF was prepared by the improved sodium metaperiodate method and nasally administrated to the β-amyloid protein(Aβ25-35) induced amnesic mice for 7 days with 2 dosage (7-5 μg/d、15 μg/d). Spatial learning and memory abilities were evaluated by Morris water maze and cholinergic function was assessed with the choline acetyl transferase (ChAT) immunohistochemical methods.ResultsMorris water maze test showed that the escape latency in Aβ25-35-treated mice prolonged and the staying time reduced in the crossed first quadrant where the platform had been located, compared with the control mice (P<0-01). In addition, the number of ChAT positive neuron declined in the model mice(P<0-001). CB-NGF nasal administration significantly shortened the escape latency and elevated the staying time and number of ChAT positive neuron(P<0-01).ConclusionCB-NGF treatment can improve the spatial and memory performance which may involve the neuroprotection to cholinergic system.

Key words: cholera toxin B subunit, nerve growth factor, β-amyloid protein, Morris water maze, choline acetyl transferase