脓毒症中性粒细胞多模态死亡方式的分子机制及中医药干预策略研究进展

The regulatory mechanism of multimodal death of neutrophils in the pathological process of sepsis

关键词:  中性粒细胞死亡  脓毒症  坏死  凋亡  自噬  焦亡  NETosis  中医药

Key words:  neutrophil death  sepsis  necrosis  apoptosis  autophagy  pyroptosis  NETosis  traditional Chinese medicine

摘要:

脓毒症是由宿主对感染的免疫反应失调所致的危及生命的器官功能障碍。中性粒细胞作为先天免疫防御的第一道防线，不仅通过吞噬病原体、释放炎性细胞因子、活性氧（ROS）及抗菌物质等方式发挥抗感染作用，其死亡方式的调控也与脓毒症的病理进程密切相关。在脓毒症状态下，中性粒细胞的凋亡受到显著抑制，导致其寿命异常延长，同时伴随迁移能力下降，并可能转向其他类型的细胞死亡，如坏死性凋亡、中性粒细胞胞外捕获物（NETosis）等，进而加剧炎症反应与组织损伤。文章系统综述了中性粒细胞的多模态死亡方式在脓毒症发生发展中的已知影响以及中医药靶向中性粒细胞治疗脓毒症的策略研究进展，旨在为深入阐明脓毒症的病理生理学特征及开发靶向治疗策略提供新的理论视角和研究思路。

Abstract:

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host immune response to infection. Neutrophils，as the first line of innate immune defense，play a critical role in combating infections through phagocytosis of pathogens，release of inflammatory cytokines，reactive oxygen species（ROS），and antimicrobial substances. The regulation of neutrophil death modes is also closely linked to the pathological progression of sepsis. In the context of sepsis，neutrophil apoptosis is significantly inhibited，leading to abnormal prolongation of their lifespan，accompanied by impaired migration capacity and a potential shift toward other forms of cell death，such as necroptosis and NETosis，thereby exacerbating inflammatory responses and tissue damage. This article systematically reviews the known impacts of multimodal neutrophil death modes on the development of sepsis and the research progress in traditional Chinese medicine（TCM）strategies targeting neutrophils for sepsis treatment. The aim is to provide new theoretical perspectives and research directions for elucidating the pathophysiological characteristics of sepsis and developing targeted therapeutic strategies.