中国组织工程研究 ›› 2012, Vol. 16 ›› Issue (46): 8641-8646.doi: 10.3969/j.issn.2095-4344.2012.46.018

• 组织构建与生物活性因子 tissue construction and bioactive factors • 上一篇    下一篇

神经生长因子预处理阿尔茨海默病大鼠海马神经原磷酸化Tau蛋白的变化

马惠萍1,吕心瑞2,史鸿云3,石镇霞2,李新春1,李 峥4   

  1. 1开封市卫生学校解剖教研室,河南省开封市 475003
    2河南大学医学院生理教研室,河南省开封市 475003
    3河北大学附属医院,河北省保定市 071000
    4四川大学华西口腔医学院,四川省成都市 610000
  • 收稿日期:2012-02-26 修回日期:2012-03-26 出版日期:2012-11-11 发布日期:2012-11-11
  • 通讯作者: 李新春,高级讲师,开封市卫生学校解剖教研室,河南省开封市 475003
  • 作者简介:马惠萍,女,1964年生,河南省开封市人,汉族,2003年武汉科技大学毕业,副主任医师,高级讲师,主要从事口腔解剖生理学研究。 mhp05@126.com

Effect of nerve growth factor pretreatment on phosphorylated Tau protein expression in hippocampal neurons in Alzheimer’s disease rats

Ma Hui-ping1, Lü Xin-rui2, Shi Hong-yun3, Shi Zhen-xia2, Li Xin-chun1, Li Zheng4   

  1. 1Anatomy Room, Kaifeng Medical School, Kaifeng 475003, Henan Province, China
    2Physiology Room, Medical College of Henan University, Kaifeng 475003, Henan Province, China
    3The Affiliated Hospital of Hebei University, Baoding 071000, Hebei Province, China
    4West China School of Stomatology, Sichuan University, Chengdu 610000, Sichuan Province, China
  • Received:2012-02-26 Revised:2012-03-26 Online:2012-11-11 Published:2012-11-11
  • Contact: Li Xin-chun, Senior Lecturer, Anatomy Room, Kaifeng Medical School, Kaifeng 475003, Henan Province, China
  • About author:Ma Hui-ping, Associate chief physician, Anatomy Room, Kaifeng Medical School, Kaifeng 475003, Henan Province, China mhp05@126.com an,

摘要:

背景:神经生长因子能够促进胆碱能神经元的分化,决定轴突的生长,并可参与损伤神经的再生和功能修复。
目的:进一步验证神经生长因子预处理对拟阿尔茨海默病模型大鼠脑内神经原纤维缠结和磷酸化Tau蛋白表达的影响。
方法:将3-5月龄雄性Wistar大鼠随机分为3组:模型组将冈田酸微量注射至拟大鼠海马CA1区建立拟阿尔茨海默病大鼠模型;预处理组于造模前将神经生长因子注射至侧脑室;对照组用同样方法注入等体积的二甲亚砜作为对照。通过Morris水迷宫观察上述大鼠的行为学变化,分别用改进的Bielschowsky染色观察海马CA1区神经原纤维缠结,用免疫组织化学和免疫印迹法观察海马区磷酸化Tau蛋白表达的变化。
结果与结论:拟阿尔茨海默病模型组大鼠出现认知、学习记忆能力减退;与对照组比较,模型组海马CA1区出现较多神经原纤维缠结, 而且磷酸化的Tau蛋白表达增多;神经生长因子预处理组大鼠的上述症状明显改善。提示神经生长因子预处理可以显著改善拟阿尔茨海默病模型大鼠的学习记忆能力,抑制神经原纤维缠结的形成,减少磷酸化Tau蛋白的表达。

关键词: 神经生长因子, 阿尔茨海默病, 神经纤维原缠结, 磷酸化Tau蛋白

Abstract:

BACKGROUND: Nerve growth factor (NGF) can promote the differentiation of cholinergic neuron, determine the growth of axons and involve in the regeneration and functional recovery of injured nerve.
OBJECTIVE: To further validate the effects of NGF pretreatment on neurofibrillary tangles (NFT) and phosphorylated Tau protein expression in the hippocampal CA1 region of Alzheimer’s disease (AD)-like model rats.
METHODS: Male Wistar rats (3-5 months old) were randomly divided into control group, AD-like model group and NGF pretreatment group. In the AD-like model group, AD-like rat model was established by injecting okadaic acid into the hippocampal CA1 region. In the NGF pretreatment group, NGF was injected into the lateral ventricle of the brain in rats before okadaic acid was injected for establishing the AD-like animal model. The rats of the control group were injected an equal volume of dimethyl sulfoxide using the same method. The behavior changes of rats were observed by Morris water maze. Then, the NFT in hippocampal CA1 region was detected by improved Bielschowsky staining. Besides, the changes of phosphorylated Tau protein expression in the hippocampal CA1 region were observed by immunohistochemical and western blot methods.
RESULTS AND CONCLUSION: Learning disabilities and memory deficits in the AD-like model rats were found. Compared with the control group, in the model group, there were more NFTs; in addition, the phosphorylated Tau protein expression was increased in the hippocampus. However, the above symptoms in the rats of the NGF pretreated group were improved obviously. These results suggest that NGF pretreatment can significantly improve learning and memory capabilities of the AD-like model rats, inhibit NFT formation and decrease the expression of phosphorylated Tau protein.

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