Aβ诱导的氧化应激损伤是阿尔茨海默病(AD)主要发病机制之一，氧化应激也是诱导线粒体自噬的主要原因，α7 nAChRs可通过对抗Aβ诱导的氧化应激发挥其神经保护作用。我们前期研究发现，α7 nAChR的激动对线粒体自噬具有调控作用，可对抗Aβ对线粒体自噬的影响，但是其具体作用及机制尚不明确。本申请课题从线粒体自噬角度出发，以APP/PS1转基因鼠为研究对象，研究大脑Aβ的聚集对皮层及海马氧化应激、线粒体自噬水平及自噬相关通路的影响，且随着Aβ聚集加重，氧化应激水平、线粒体自噬与Aβ聚集程度的相关性；特异性激动转基因鼠大脑α7 nAChRs后上述测定指标的变化；同时在原代培养海马神经元中研究α7 nAChRs对抗Aβ对细胞氧化应激水平、线粒体自噬水平及相关通路的影响，为进一步阐明AD发病机制及α7 nAChRs神经保护机制提供可靠的理论依据，为痴呆的治疗提供治疗靶点依据。

Aβ-induced oxidative stress injury is one of the major pathogenesis of Alzheimer's disease (AD) and is also the main reason for inducing mitochondrial autophagy. α7 nAChRs exert their neuroprotective effect by antagonizing Aβ-induced oxidative stress. Our previous study found that the activation of α7 nAChR regulates mitochondrial autophagy and antagonizes the effects of Aβ on mitochondrial autophagy, but the mechanism remains unclear. This study is to investigate these unsolved problems by using APP/PS1 transgenic mouse as research object to study the effects of brain Aβ aggregation on oxidative stress, mitochondrial autophagy and autophagy-related pathways in cortical and hippocampal. And to study that with the aggravation of Aβ, the association among the level of oxidative stress, the mitochondrial autophagy and Aβ aggregation. The research also focused on the changes of the above measured indexes after specific activation of α7 nAChRs of the APP/PS1 transgenic mice. At the same time, primary cultured hippocampal neurons were used to study the effects of α7 nAChRs agonist on the level of oxidative stress, mitochondrial autophagy and related pathways induced by Aβ. The obtaining results in the study will provide a reliable theoretical basis for further elucidating the pathogenesis of AD and the neuroprotective mechanism of α7 nAChRs.