卒中后NETs介导免疫血栓的形成机制及神经血管损伤的研究进展OA
Research progress on mechanism of NETs-mediated immunothrombosis and neurovascular injury after stroke
免疫血栓是导致卒中后微循环障碍,加重炎症反应的重要病理产物.该文聚焦免疫血栓的核心骨架——中性粒细胞胞外诱捕网(neutrophil extracellular traps,NETs),阐述了卒中后NETs的形成信号,包括活性氧(reactive oxygen spe-cies,ROS)风暴、损伤相关分子模式释放、炎症因子增加等,探讨了其形成的关键机制,如肽基精氨酸脱亚胺酶4(pepti-dylarginine deiminase 4,PAD4)介导的组蛋白瓜氨酸化、ROS信号通路、颗粒蛋白酶的作用,还分析了NETosis的不同类型.进一步分析了NETs通过直接损伤血脑屏障与神经胶质细胞、放大炎症反应,加重神经血管单元损伤,进而相互促进形成恶性循环.在此基础上,总结了靶向NETs的临床前治疗策略,为脑卒中治疗提供新靶点与理论依据.
Immunothrombosis is an important pathological prod-uct that leads to microcirculation disturbance and aggravation of inflammatory response after stroke.This article focuses on neu-trophil extracellular traps(NETs),the core skeleton of immune thrombosis,and expounds the formation signals of NETs after stroke,including reactive oxygen species(ROS)storm,damaging-related molecular patterns release,and increased in-flammatory factors,and explores the key mechanism of its for-mation,such as peptidyl-arginine deiminase 4(PAD4)-medi-ated histone citrullination,ROS signaling pathway,granzyme,and analyzed the different types of NETosis.Furthermore,NETs directly damage the blood-brain barrier and glial cells,amplify the inflammatory response,and aggravate the damage of the neurovascular unit,thereby promoting each other to form a vicious circle.On this basis,we summarize the preclinical treatment strategies of NETs,providing new targets and theoreti-cal basis for the treatment of stroke.
屈山河;阮元;张天怡;楚世峰;陈乃宏
广东药科大学中药学院,广东 广州 510006中国医学科学院药物研究所,北京 100050中国医学科学院药物研究所,北京 100050中国医学科学院药物研究所,北京 100050广东药科大学中药学院,广东 广州 510006||中国医学科学院药物研究所,北京 100050
医药卫生
免疫血栓NETs中性粒细胞脑卒中血小板炎症
immunothrombosisNETsneutrophilsstrokeplateletsinflammation
《中国药理学通报》 2026 (8)
1401-1406,6
国家自然科学基金资助项目(No U2202214)
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