NLRP3炎性小体在脊髓损伤后小胶质细胞中的作用  

Effect of NLRP3 inflammasome in microglia after spinal cord injury

作　　者：周文洋 廖烨晖 田明昊 何宝强 钟德君 Zhou Wenyang;Liao Yehui;Tian Minghao;He Baoqiang;Zhong Dejun(Department of Orthopedics,Affiliated Hospital of Southwest Medical University,Luzhou 646000,Sichuan Province,China)

机构地区：[1]西南医科大学附属医院骨科,四川省泸州市646000

出　　处：《中国组织工程研究》2025年第13期2849-2860,共12页Chinese Journal of Tissue Engineering Research

基　　金：四川省医学会科研课题计划(S17075),项目负责人:钟德君;泸州市人民政府——西南医科大学科技战略合作项目(2020LZXNYDJ22),项目负责人:钟德君。

摘　　要：背景:NOD样受体热蛋白结构域相关蛋白3(NOD-like receptor thermal protein domain associated protein 3,NLRP3)炎性小体与脊髓损伤后的神经炎症密切相关,小胶质细胞极化和焦亡在其中发挥关键作用,靶向调控NLRP3有利于诱导小胶质细胞从M1促炎表型向M2抗炎表型极化和调节小胶质细胞焦亡,是一个有前景的治疗策略。目的:归纳NLRP3炎性小体在脊髓损伤后小胶质细胞中作用的分子机制以及治疗策略的研究进展。方法:检索PubMed、Web of Science和中国知网数据库,英文检索词为“spinal cord injury,NLRP3,microglia,polarization,pyroptosis”,中文检索词为“脊髓损伤,NLRP3,小胶质细胞,极化,焦亡,炎症”,按纳入和排除标准共纳入79篇文献进行总结。结果与结论:①目前,关于脊髓损伤复杂的发病机制尚未有统一定论,大量研究表明脊髓损伤与炎症因子和信号通路关系密切,以NLRP3炎性小体作为其发病机制和治疗突破口的相关研究也是当前的热点。②NLRP3炎性小体在脊髓损伤后的炎症反应、氧化应激和神经元恢复等起到关键作用。③小胶质细胞是脑和脊髓中的免疫细胞,是继发性脊髓损伤最重要的调节因子,脊髓损伤后小胶质细胞对内部环境作出调整,主要表现为极化及焦亡,产生大量炎症因子,阻碍脊髓损伤的神经再生和功能恢复,通过调控小胶质细胞表型变化,是治疗脊髓损伤的另一个关键因素。④NLRP3炎性小体与小胶质细胞密切相关,脊髓损伤后NLRP3炎性小体主要在小胶质细胞中表达,其会促进小胶质细胞向M1极化和促进促裂解蛋白D的产生,进一步破坏神经稳态,从而加重脊髓损伤的进展。⑤许多分子参与NLRP3炎性小体调控小胶质细胞,其中核转录因子κB及MAPK信号通路促进NLRP3炎性小体表达,其他信号通路抑制该炎性小体表达。⑥目前有大量的外源性分子及药物调控NLRP3炎性小体,临床应用前景广泛,已�BACKGROUND:NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome is closely related to neuroinflammation after spinal cord injury,in which microglial polarization and pyroptosis play a key role.Targeted regulation of NLRP3 can induce microglial polarization from M1 proinflammatory phenotype to M2 anti-inflammatory phenotype and regulate microglial pyroptosis,which is a promising therapeutic strategy.OBJECTIVE:To summarize the molecular mechanism and therapeutic strategies of NLRP3 inflammasome in microglia after spinal cord injury.METHODS:Databases of PubMed,Web of Science,and CNKI were searched for the articles with search terms“spinal cord injury,NLRP3,microglia,polarization,pyroptosis”in English and“spinal cord injury,NLRP3,microglia,polarization,pyroptosis,inflammation”in Chinese.Finally,a total of 79 articles were included according to the inclusion and exclusion criteria.RESULTS AND CONCLUSION:(1)Currently,there is no consensus on the complex pathogenesis of spinal cord injury.A large number of studies have shown that spinal cord injury is closely related to inflammatory factors and signaling pathways.The NLRP3 inflammasome is a hot topic in current research as a mechanism of disease and a breakthrough in treatment.(2)The NLRP3 inflammasome plays a key role in the inflammatory response,oxidative stress,and neuronal recovery after spinal cord injury.(3)Microglia are immune cells in the brain and spinal cord and are the most important regulatory factors in secondary spinal cord injury.After spinal cord injury,microglia adjust the internal environment,mainly manifested as polarization and necrosis,produce a large number of inflammatory factors,hinder the nerve regeneration and functional recovery of spinal cord injury,and regulating the phenotype change of microglia is another key factor in the treatment of spinal cord injury.(4)The NLRP3 inflammasome is closely related to microglia.After spinal cord injury,NLRP3 is mainly expressed in microglia,which promotes the polarizatio

关 键 词：脊髓损伤 NLRP3 小胶质细胞 极化 焦亡 炎症 非编码RNA 中药活性成分 干细胞 特异性抑制剂 

分 类 号：R459.9[医药卫生—治疗学] R363[医药卫生—临床医学] R364