电针通过调控多重信号通路干预阿尔茨海默病的整合机制研究综述

Electroacupuncture Modulates Multiple Signaling Pathways in Alzheimer’s Disease: A Review of Integrated Mechanisms

摘要: 阿尔茨海默病(Alzheimer’s disease, AD)是一种渐进性神经退行性疾病，以认知功能障碍为主要特征，其发病机制涉及β-淀粉样蛋白(Aβ)沉积、Tau蛋白过度磷酸化、神经炎症、氧化应激等多重病理过程。电针作为一种传统中医疗法，在AD治疗中展现出多靶点、整体调节的优势。本综述系统整合了近年来的实验研究文献，重点探讨电针通过调控多重信号通路干预AD的整合机制。文献分析表明，电针可作用于外周和中枢系统，通过调节神经营养与突触可塑性通路(如PI3K/Akt、BDNF/TrkB)、炎症相关通路(如NF-κB、NLRP3)、代谢与能量相关通路(如PGC-1α/Irisin/BDNF)、以及其他关键通路(如Wnt/β-catenin、Notch)等，改善AD模型动物的学习记忆能力，抑制神经炎症、促进神经再生、增强突触可塑性。不同研究从神经营养、炎症、代谢等角度揭示了电针作用的互补性：例如，电针可能通过激活PI3K/Akt通路直接增强突触可塑性，同时抑制NF-κB通路减轻炎症；而电针通过影响代谢通路上调鸢尾素则间接支持BDNF表达。这些通路并非孤立存在，而是通过复杂的网络相互作用，共同构成电针干预AD的整合机制。本综述还讨论了当前研究的局限性，如动物模型差异、针刺参数标准化问题，并展望未来需结合多组学技术和临床实验深化研究。

Abstract: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder primarily characterized by cognitive dysfunction. Its pathogenesis involves multiple pathological processes, including β-amyloid (Aβ) deposition, hyperphosphorylation of Tau protein, neuroinflammation, and oxidative stress. Electroacupuncture (EA), as a therapeutic modality within traditional Chinese medicine, demonstrates advantages in multi-target and holistic regulation in the treatment of AD. This review systematically integrates recent experimental research literature, focusing on the integrated mechanisms by which EA intervenes in AD through the regulation of multiple signaling pathways. Analysis of the literature indicates that EA acts on both peripheral and central systems. It ameliorates learning and memory abilities in AD animal models, inhibits neuroinflammation, promotes neuroregeneration, and enhances synaptic plasticity by modulating various pathways. These include neurotrophic and synaptic plasticity pathways (e.g., PI3K/Akt, BDNF/TrkB), inflammation-related pathways (e.g., NF-κB, NLRP3), metabolism and energy-related pathways (e.g., PGC-1α/Irisin/BDNF), and other key pathways (e.g., Wnt/β-catenin, Notch). Research from various perspectives—neurotrophic, inflammatory, metabolic, and others—reveals complementary mechanisms of EA action. For instance, EA may directly enhance synaptic plasticity by activating the PI3K/Akt pathway while concurrently alleviating neuroinflammation by suppressing the NF-κB pathway. Furthermore, the upregulation of irisin through metabolic pathways may indirectly support BDNF expression. These pathways do not operate in isolation but interact through complex networks, collectively constituting the integrated mechanism of EA intervention in AD. This review also discusses limitations of current research, such as differences in animal models and lack of standardization in acupuncture parameters, and suggests that future studies should integrate multi-omics technologies and clinical trials to deepen the understanding of these mechanisms.