《生命科学》 2026, 38(5): 769-782

NLRP3炎性小体在脑缺血及相关疾病中的研究进展

刘倩倩^1,2 , 王 可³ , 王延伟³ , 兰 平^1,2 , 何 治^1,2,3,*

¹三峡大学国家中医药管理局中药药理科研三级实验室，宜昌 443002 ²三峡大学健康医学院，宜昌 443002 ³嘉兴大学医学院，嘉兴 314000

摘　要：

NOD样受体热蛋白结构域相关蛋白3（NOD-like receptor pyrin domain containing 3，NLRP3）炎性小体是可识别细菌毒素、线粒体活性氧等内源性及外源性危险信号的多蛋白复合物，在天然免疫与炎症反应调节中起核心作用。近年，NLRP3 成为脑缺血领域研究热点，其激活与脑卒中后脑部炎症微环境密切相关，通过介导炎症反应、氧化应激、细胞焦亡等过程，显著加剧缺血性脑损伤。本文将系统综述NLRP3结构、功能与激活途径，重点探讨其在脑缺血病理进程中的作用及分子机制，为脑缺血免疫治疗策略制定及药物靶点开发提供理论依据。

通讯作者：何 治 , Email:hezhi@ctgu.edu.cn

Research progress of NLRP3 inflammasome in cerebral ischemia andrelated diseases

LIU Qian-Qian^1,2 , WANG Ke³ , WANG Yan-Wei³ , LAN Ping^1,2 , HE Zhi^1,2,3,*

¹Third-grade Pharmacological Laboratory on Traditional Chinese Medicine, State Administration of Traditional Chinese Medicine, China Three Gorges University, Yichang 443002, China ²School of Health Medicine, China Three Gorges University, Yichang 443002, China ³School of Medicine, Jiaxing University, Jiaxing 314000, China

Abstract:

The NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome is a multiprotein complex that recognises endogenous and exogenous danger signals such as bacterial toxins and mitochondrial reactive oxygen species, playing a central role in innate immunity and the regulation of inflammatory responses. In recent years, NLRP3 has emerged as a key molecule in the field of cerebral ischaemia, with its activation closely associated with the post-stroke cerebral inflammatory microenvironment. In the context of cerebral ischemia, NLRP3 plays a critical role in neuropathology. Following ischemic stroke, NLRP3 is activated by multiple upstream signals, including the TLR4/NF-κB pathway, reactive oxygen species (ROS), mitochondrial damage, release of mitochondrial DNA (mtDNA), and calcium overload. Through these activation pathways, NLRP3 mediates key pathological  processes such as proinflammatory cytokine release (e.g., IL-1β and IL-18), pyroptosis (inflammatory cell death), and oxidative stress.  These events directly increase cerebral infarct volume, disrupt the integrity of the bloodbrain barrier (BBB), and exacerbate  neurological deficits, leading to poor functional outcomes. Moreover, NLRP3 serves as a pivotal hub in the crosstalk between the central nervous system and peripheral inflammatory responses. It can indirectly influence the prognosis of cerebral ischemia by modulating peripheral pathological processes. Specifically, NLRP3 contributes to the development and progression of major cerebral ischemia risk factors, including atherosclerosis, glucose metabolism disorders (e.g., diabetes), and gut-brain axis dysregulation (such as gut microbiota dysbiosis). Conversely, targeted inhibition of the NLRP3 inflammasome not only blocks the central inflammatory cascade but also ameliorates these peripheral risk factors, thereby reducing the risk and severity of cerebral ischemia fundamentally.  Therefore, therapeutic strategies aimed at inhibiting the NLRP3 inflammasome—whether by blocking its activation pathways, enhancing mitochondrial autophagy, regulating noncoding RNAs, or by administering small molecule inhibitors or natural medicines—can simultaneously address both central nervous system inflammation and peripheral comorbidities. Such dual target approaches trategies are highly promising for substantially reducing ischemic brain injury and enhancing poststroke recovery.

Communication Author：HE Zhi , Email:hezhi@ctgu.edu.cn