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从“能量障碍-炎症”交互影响的Akt/PGC-1α/NLRP3通路探讨地黄饮子治疗AD的补肾化痰作用

从“能量障碍-炎症”交互影响的Akt/PGC-1α/NLRP3通路探讨地黄饮子治疗AD的补肾化痰作用
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  • 批准号:81673929
  • 批准年度: 2016年
  • 学科分类:中医内科(H2708) |
  • 项目负责人:马涛
  • 负责人职称:副研究员
  • 依托单位:北京中医药大学
  • 资助金额:58万元
  • 项目类别:面上项目
  • 研究期限:2017年01月01日 至 2020年12月31日
  • 中文关键词: Akt/PGC-1α/NLRP3;地黄饮子;治疗;补肾;化痰
  • 英文关键词:Alzheimer disease;Kidney-invigorating and Phlegm-eliminating;energy disturbance;inflammation;Akt/PGC

项目摘要

中文摘要

近年研究证实,Akt/PGC-1α/NLRP3通路介导的“能量障碍-炎症”相互为恶的交互作用,是阿尔茨海默病(AD)病程启动与恶化的核心环节,为AD重要治疗靶标。“补肾化痰”方药地黄饮子基于AD“肾虚痰阻”病机进行治疗,效果显著。我们前期发现,地黄饮子通过调控Akt和NF-κB,改善AD小鼠脑能量障碍和炎症损伤。由此推论“地黄饮子由Akt/PGC-1α/NLRP3通路阻断能量障碍-炎症交互作用引发的恶性循环,发挥抗AD‘补肾化痰’功效”。本项目围绕地黄饮子对能量障碍-炎症交互作用的干预机理及其对Akt/PGC-1α/NLRP3调控机制的研究,结合体内外实验,整合神经影像和分子生物学技术,从能量、炎症、突触结构、细胞凋亡、认知等多个角度,在整体、组织、细胞分子等多水平上研究地黄饮子对能量障碍-炎症交互作用的整合调控机制,以新的视角阐释地黄饮子抗AD机理,丰富发展中医理论,探索AD治疗新突破。

英文摘要

Recent studies have confirmed that “energy disturbance and inflammation” interaction via Akt/PGC-1α/NLRP3 pathway drived the course and deterioration of Alzheimer's disease (AD), and served as an important therapeutic targets for the AD. "Kidney-invigorating and Phlegm-eliminating" prescription named Dihuang Yinzi has been used in treatment in AD based on " Kidney-debility and Phlegm-stuck" pathogenesis, and the clinical effect is significant. Our previous study showed that Dihuang Yinzi could ameliorate energy impairment and inflammatory damage in AD mouse by modulating Akt and NF-κB. We speculate that "Dihuang Yinzi exerts anti-AD 'Kidney-invigorating and Phlegm-eliminating' effect by blocking the vicious cycle of inflammation/energy via Akt/PGC-1α/NLRP3 pathway". The current project will performed by focusing on intervention mechanisms of energy/inflammation and its effect on Akt/PGC-1α/NLRP3, with in vivo and in vitro experiments, by the way of the integrating neuroimaging and molecular biology techniques, from various angles of energy, inflammation, synaptic structure, apoptosis, cognition, etc. We will investigate integrated modulation of Dihuang Yinzi on the interaction of energy/inflammation at multiple levels of animal, tissues, cell, and molecular, to develop the theory of traditional Chinese medicine, and explore the breakthroughs of the treatment of AD.

评估说明

    国家自然科学基金项目“从“能量障碍-炎症”交互影响的Akt/PGC-1α/NLRP3通路探讨地黄饮子治疗AD的补肾化痰作用”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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