基于Parkin活化探讨“通督启神”法电针调控线粒体自噬干预AD小鼠的脑保护机制

申请人前期发现电针可以降低Aβ水平改善AD小鼠的学习记忆能力（ECAM，2016），并观察到AD小鼠中的自噬空泡及线粒体等囊性细胞器（神经解剖学杂志，2015）。最新研究显示:线粒体自噬可抑制Aβ沉淀逆转AD的认知缺陷。本课题选用转基因APP/PS1小鼠作为研究对象，从与线粒体自噬密切相关的Parkin活化相关靶点入手，应用Micro-PET、激光共聚焦、免疫组化、Western blot多种技术，从“在体-组织-分子”三个层次进行研究，观察电针对AD小鼠Aβ表达和线粒体自噬的干预效应，分析不同脑区线粒体自噬及Parkin活化关键靶点，明确Parkin活化在电针调控线粒体自噬中的关键作用。以验证“电针通过激活Parkin增加线粒体自噬保护脑神经元，减少Aβ沉淀，从而改善AD小鼠的学习记忆能力”的假说，力求从分子生物学角度阐释电针干预AD的作用机制，为临床治疗AD开辟新的途径并提供科学依据。

It was previously found that electroacupuncture could decrease the level of Aβ and improve the learning and memory ability in AD mice (ECAM,2016). Further more, autophagy vacuoles and mitochondria were observed in the AD mice (Journal of Neuroanatomy, 2015). New research shows that mitophagy inhibits Aβ reverses cognitive deficits in AD. In this study, APP/PS1 mice were selected as the research object. The Parkin pathway closely related to mitophagy was studied. Micro-PET, laser confocal and immunohistochemical, Western blot techniques were used. The intervention effects of electroacupuncture on AD mice Aβ and mitophagy were observed from three levels of "in vivo-tissue-molecule". The key targets of mitophagy and Parkin activation in different brain regions were detected and analyzed. The key role of Parkin activation in mitochondrial autophagy was elucidated. In order to verify the hypothesis that ‘electroacupuncture can improve the ability of learning and memory of AD model by activating Parkin to increase mitophagy to protect brain neurons and reduce Aβ precipitation’, we try to explain the mechanism of electro-acupuncture intervention in AD from the point of molecular biology. Therefore to develop a new clinical treatment method for AD and provide its experimental basis.