细胞焦亡在肠缺血再灌注损伤中作用的研究进展

Research progress on the role of pyroptosis in intestinal ischemia-reperfusion injury

细胞焦亡是一种可导致炎症反应的程序性细胞死亡,其发生依赖于炎症小体、炎性半胱天冬酶(caspase)等蛋白相继激活进而裂解消皮素D(gasdermin D, GSDMD)蛋白使其N端在细胞膜多聚化并产生焦亡小孔。细胞焦亡的发生有炎症小体激活caspase-1的经典途径和胞质LPS激活caspase-4/5/11的非经典途径;作为介导机体炎症反应的重要机制,细胞焦亡在机体应对伤害性刺激的反应中具有不可替代的作用,其与神经系统疾病、心血管系统疾病和肿瘤等多种疾病密切相关。最近研究发现,细胞焦亡在肠缺血再灌注损伤(intestinal ischemia-reperfusion injury, Ⅱ/RI)的发生中也具有关键作用,本文就近年来细胞焦亡的分子特征、机制与Ⅱ/RI的关系进行综述,旨在为Ⅱ/RI的防治提供理论依据。

Pyroptosis is a newly discovered programmed cell death that can lead to inflammatory response,its occurrence depends on the sequential activation of inflammatory bodies and caspase,and then the pore-forming generated by the fragmentation of gasdermin D and its cell membrane polymerization.Pyroptosis is mainly comprised of the pathway that depends on caspase-1 activated by flammasomes and the non-classical pathway that depends on caspase-4/5/11 activated by cytoplasmic lipopolysaccharide.As an important mechanism mediating the inflammatory response of the body,pyroptosis plays an irreplaceable role in the body’s response to noxious stimuli,which is closely related to many diseases such as nervous system diseases,cardiovascular system diseases and tumors.Recent studies have found that pyroptosis also plays a key role in the occurrence of intestinal ischemia-reperfusion(Ⅱ/RI).This paper reviews the molecular characteristics,mechanism of pyroptosis and its relationship withⅡ/RI in recent years,in order to provide theoretical basis for the prevention and treatment ofⅡ/RI.