基于P2X7R/NLRP3/Caspase-1通路探讨耳甲γ频率电针改善APP/PS1小鼠认知的作用与机制

耳穴疗法是中医针灸的重要组成部分。耳甲区是哺乳类动物体表唯一有迷走神经传入纤维分布的区域，即分布于耳甲的迷走神经耳支是可通达中枢神经系统的一条特殊周围通路。迷走神经刺激（VNS）对阿尔茨海默病（AD）有效。基于耳穴疗法、神经解剖学、VNS而产生的经耳迷走神经刺激（taVNS）对脑病能起到与传统VNS相近的效果。γ频率（40Hz）刺激可逆转AD是近年重大发现之一。多种γ频率刺激均能逆转AD相关病理并能改善AD模型小鼠的认知行为表现。近年来，神经炎症渐已成为AD研究的新热点，抑制神经炎症或是治疗AD的有效策略。故本研究将致力于：1、探索40Hz-taVNS对9月龄APP/PS1小鼠认知行为的改善作用；2、从与神经炎症密切相关的P2X7R/NLRP3/Caspase-1通路入手，为40Hz-taVNS逆转AD找到可能的机制；3、为40Hz-taVNS未来在AD患者的临床研究提供可靠的实验室证据。

Auriculotherapy is an essential component of acupuncture in TCM. The auricular conchae is the only superficial area in mammals with vagal nerve afferent fibers distribution, which suggested that the auricular branch of the vagal nerve distributed in the auricular concha is a unique peripheral pathway to the central nervous system (CNS). Some studies have confirmed that vagal nerve stimulation (VNS) is effective for Alzheimer's disease (AD). Transcutaneous auricular vagal nerve stimulation (taVNS), which was developed based on auriculotherapy, neuroanatomy, and VNS, conducts comparable efficacy to classic VNS. Gamma frequency (40Hz) entrainment can reverse AD, which is a significant discovery in recent years. Various gamma-frequency stimulations can reverse AD-related pathologies and improve the cognitive behaviors in AD model mice. In recent years, neuroinflammation has gradually become a new focus in the AD researching field; suppressing neuroinflammation may be an effective strategy for treating AD. Thus, in this study, our goals are: 1. to explore the effects of 40Hz-taVNS on 9-month-old APP/PS1 mice; 2. to find the possible mechanisms through the P2X7R/NLRP3/Caspase-1 pathway, which is closely related to neuroinflammation; 3. to provide preliminary experimental evidence for further clinical studies of using 40Hz-taVNS in AD patients.