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艾灸督脉清除APP/PS1双转基因小鼠Aβ的自噬调控机制研究

艾灸督脉清除APP/PS1双转基因小鼠Aβ的自噬调控机制研究
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  • 批准号:81603701
  • 批准年度: 2016年
  • 学科分类:中医针灸(H2718) |
  • 项目负责人:朱才丰
  • 负责人职称:副主任医师
  • 依托单位:安徽中医药大学
  • 资助金额:17万元
  • 项目类别:青年科学基金项目
  • 研究期限:2017年01月01日 至 2019年12月31日
  • 中文关键词: APP/PS1;双转基因;小鼠;Aβ;自噬
  • 英文关键词:moxibustion;Alzheimer disease;β-amyloid protein;signaling pathway ;autophagy

项目摘要

中文摘要

艾灸督脉具有通督益肾、生髓健脑、开窍调神功效,临床研究发现其治疗AD前期疗效确切。脑内Aβ沉积是AD发病的中心环节,细胞自噬是清除有害的Aβ的重要途径,调控细胞自噬促进Aβ清除,是治疗AD的关键靶点,据此提出“艾灸督脉通过调控PI3K/Akt/mTOR通路诱导自噬清除Aβ蛋白从而改善认知功能障碍”的科学假说。本实验通过观察艾灸督脉对AD转基因小鼠行为学评分、事件相关电位、海马Aβ、与自噬有关的蛋白(LC3-I ,LC3-II,自噬底物蛋白P62, Beclin 1,Bcl-2)以及电镜观察神经元内自噬泡的含量变化,获取艾灸督脉改善认知功能、诱导自噬清除Aβ的直接证据;通过检测PI3K、AKT、p-AKT 、mTOR、p-mTOR蛋白表达来探明该灸法是否通过调控PI3K/Akt/mTOR通路来上调自噬,促进Aβ清除,深入阐释艾灸督脉治疗AD的作用机理,旨在为该灸法临床应用提供重要的理论依据。

英文摘要

Moxibustion on DU meridian points was a treating method of Alzheimer's disease (AD), which can activate Du meridian and regulate the mind . Preliminary clinical study have confirmed that it is quite effective in improving learning ability and memory.. As widely accepted, β-amyloid protein (Aβ) plays a central role in AD pathogenesis. The abnormal release and deposition of Aβ is the initiating factor to form senile plaque and the important components of its core. Autophagy, the basic intracellular mechanism for catabolic and continuous clearance of unnecessary or dysfunctional components, occupies a crucial role in AD . Amyloid⁃β protein (Aβ) can be eliminated during autophagy. Observation will be made on the effects of event-related potentials (ERP)on the AD transgenic mice behavior during water maze test. Western blot will be applied to analyze the autophagy-related protein levels of LC3-I, LC3-II and the autophagy substrate P62. To verify whether mTOR signal pathway was involved in autophagy infuenced by moxibustion,the effect on phosphorylation of the mTORCl substrate p70 will be investigated. For further determination of the autophagy levels in the brain of mice, transmission electron microscopy will also be used to observe autophagicvacuoles in cortical neurons from mouse. Moxibustion on DU meridian points can antagonize against β-amyloid protein induced neuronal damage and improve the learning and memory function of AD rats through regulating the expression of PI3K/Akt/mTOR signaling pathway. At present, we are attempting to elucidate the molecule mechanism of the effect of Moxibustion on DU meridian points, e.g. action target, signal transduction pathway and related gene expression, in order to provide a more extensive theoretical basis for the clinical application of this method .

评估说明

    国家自然科学基金项目“艾灸督脉清除APP/PS1双转基因小鼠Aβ的自噬调控机制研究”发布于爱科学iikx,并永久归类于相关科学基金导航中,仅供广大科研工作者查询、学习、选题参考。国科金是根据国家发展科学技术的方针、政策和规划,以及科学技术发展方向,面向全国资助基础研究和应用研究,发挥着促进我国基础研究源头创新的作用。国科金的真正价值在于它能否为科学进步和社会发展带来积极的影响。

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