小胶质细胞在中枢神经系统炎症性疾病中的作用和机制研究进展

doi:10.3969/j.issn.1674-8115.2025.05.012

摘要/Abstract

摘要：

小胶质细胞是中枢神经系统（central nervous system，CNS）中的常驻免疫细胞，其在大脑稳态维持和神经保护中发挥双刃剑的作用。在正常状态下，小胶质细胞通过监测环境变化维持大脑的稳态。当发生神经损伤或受到某些病理性刺激时，小胶质细胞会迅速激活并启动一系列复杂的免疫反应，从而引发神经炎症。小胶质细胞的适当激活可以通过抑制或清除多种病原体来保护大脑，但是过度的神经炎症则会导致神经元损伤，甚至死亡。这种炎症反应失调是多种CNS炎症性疾病（如阿尔茨海默病、帕金森病、脓毒症相关性脑病、缺血性脑卒中等）病理发展的核心特征之一。近年来，随着单细胞测序、蛋白质组学和基因编辑等技术的快速发展，针对小胶质细胞参与CNS炎症性疾病的分子机制研究取得了重要进展，尤其是在炎症小体活化、表观遗传修饰、代谢重编程等方面。然而，由于小胶质细胞在不同的病理条件下表现出异质性和双重性，临床实践上靶向小胶质细胞的治疗手段仍未能普遍应用。该文以小胶质细胞为切入点，介绍其参与CNS炎症性疾病发生发展的分子机制及靶向调控治疗策略，旨在为后续精准调控小胶质细胞功能、开发更多靶向治疗药物提供理论参考。

关键词: 小胶质细胞, 神经炎症, 中枢神经系统炎症性疾病, 致病机制, 靶向治疗

Abstract:

Microglia are the resident immune cells in the central nervous system (CNS), and play a dual role in maintaining brain homeostasis and mediating neuroprotection. Under normal conditions, microglia maintain brain homeostasis by monitoring environmental changes. When nerve damage or certain pathological stimuli occur, microglia are rapidly activated and initiate a series of complex immune responses to induce neuroinflammation. This proper activation of microglia can protect the brain by inhibiting or clearing various pathogens, but excessive neuroinflammation can lead to neuronal damage ^{and even death. This imbalance of inflammatory response is one of the core features of pathological development of many CNS inflammatory diseases, such as Alzheimer′s disease, Parkinson′s disease, sepsis-associated encephalopathy, and ischemic strokes. In recent years, with the rapid development of frontier biotechnology such as single-cell sequencing, proteinomics and gene editing, important progress has been made in understanding the molecular mechanism by which microglia participate in CNS inflammatory diseases, especially in the activation of inflammatory corpuscles, epigenetic modifications, and metabolic reprogramming. However, due to the heterogeneity and duality of microglia under different pathological conditions, therapeutic methods targeting microglia have not yet been widely used in clinical practice. In summary, this article takes microglia as the starting point and introduces the molecular mechanisms of their involvement in the occurrence and development of CNS inflammatory diseases and its targeted regulatory treatment strategy, aiming to provide theoretical reference for the subsequent precise regulation of microglia function and the development of more targeted therapeutic drugs.

Key words:
microglia,
neuroinflammation,
inflammatory diseases of central nervous system,
pathogenic mechanism,
targeted therapy

中图分类号:

R742

引用本文

禹恺, 帅哲玮, 黄洪军, 罗艳. 小胶质细胞在中枢神经系统炎症性疾病中的作用和机制研究进展[J]. 上海交通大学学报（医学版）, 2025, 45(5): 630-638.
YU Kai, SHUAI Zhewei, HUANG Hongjun, LUO Yan. Research progress on the role and mechanisms of microglia in inflammatory diseases of central nervous system[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2025, 45(5): 630-638.

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