Department of Pediatrics, Pediatric Intensive Care Unit (PICU), Shengjing Hospital of China Medical University, Shenyang, China.
Front Cell Infect Microbiol. 2022 Jul 29;12:962139. doi: 10.3389/fcimb.2022.962139. eCollection 2022.
Sepsis, a life-threatening organ dysfunction caused by a dysregulated host response to infection, is a leading cause of death in intensive care units. The development of sepsis-associated organ dysfunction (SAOD) poses a threat to the survival of patients with sepsis. Unfortunately, the pathogenesis of sepsis and SAOD is complicated, multifactorial, and has not been completely clarified. Recently, numerous studies have demonstrated that pyroptosis, which is characterized by inflammasome and caspase activation and cell membrane pore formation, is involved in sepsis. Unlike apoptosis, pyroptosis is a pro-inflammatory form of programmed cell death that participates in the regulation of immunity and inflammation. Related studies have shown that in sepsis, moderate pyroptosis promotes the clearance of pathogens, whereas the excessive activation of pyroptosis leads to host immune response disorders and SAOD. Additionally, transcription factors, non-coding RNAs, epigenetic modifications and post-translational modifications can directly or indirectly regulate pyroptosis-related molecules. Pyroptosis also interacts with autophagy, apoptosis, NETosis, and necroptosis. This review summarizes the roles and regulatory mechanisms of pyroptosis in sepsis and SAOD. As our understanding of the functions of pyroptosis improves, the development of new diagnostic biomarkers and targeted therapies associated with pyroptosis to improve clinical outcomes appears promising in the future.
脓毒症是一种由宿主对感染的失调反应引起的危及生命的器官功能障碍，是重症监护病房死亡的主要原因。脓毒症相关器官功能障碍（SAOD）的发展对脓毒症患者的生存构成威胁。不幸的是，脓毒症和 SAOD 的发病机制复杂，多因素，尚未完全阐明。最近，许多研究表明，焦亡，其特征在于炎性小体和半胱天冬酶的激活和细胞膜孔形成，参与脓毒症。与细胞凋亡不同，焦亡是一种促炎形式的程序性细胞死亡，参与免疫和炎症的调节。相关研究表明，在脓毒症中，适度的焦亡促进病原体的清除，而焦亡的过度激活导致宿主免疫反应紊乱和 SAOD。此外，转录因子、非编码 RNA、表观遗传修饰和翻译后修饰可以直接或间接调节焦亡相关分子。焦亡还与自噬、细胞凋亡、NETosis 和坏死性凋亡相互作用。本综述总结了焦亡在脓毒症和 SAOD 中的作用和调节机制。随着我们对焦亡功能的理解的提高，开发与焦亡相关的新的诊断生物标志物和靶向治疗方法以改善临床结果似乎很有前途。
