NLRP3炎性小体介导的细胞焦亡在缺血性脑卒中病理过程中的作用研究进展

Research progress on the pyroptosis mediated by the NLRP3 inflammasome in the pathology of ischemic stroke

缺血性脑卒中是严重威胁人类健康的疾病之一,目前研究发现脑组织缺血缺氧引发的细胞程序性死亡扮演着重要角色,其中,兼具细胞凋亡和坏死特点的细胞焦亡通过含pyrin结构域核苷酸结合寡聚结构域样受体家族蛋白3(NLRP3)等炎性小体介导激活,依赖胱天蛋白酶1(caspase-1)的活化及白细胞介素1β(IL-1β)和IL-18等促炎性细胞因子的释放,在缺血损伤后调控细胞生存和死亡发挥重要作用。既往研究发现,在缺血性脑卒中过程中,细胞焦亡可发生于小胶质细胞、神经元、星形胶质细胞、内皮细胞等是一种特殊的细胞死亡方式;与NLRP3等炎性小体的启动、激活密不可分,文中总结了NLRP3等炎性小体介导的细胞焦亡在缺血性脑卒中过程中的作用,探讨影响NLRP3炎性小体激活的靶点和物质,为缺血性脑卒中的治疗提供新的理论和实验依据。

Ischemic stroke is one of the diseases which pose a significant threat to human health.Recent studies have suggested that programmed cell death plays an important role in brain tissues affected by ischemia and hypoxia.Pyroptosis,which is characterized by both apoptosis and necrosis,is mediated by activation of inflammasomes,such as NOD-like receptor family,pyrin domain containing 3(NLRP3).Pyroptosis,which depends on caspase-1 activation and the release of pro-inflammatory cytokines,such as Interleukin 1βand Interleukin 18,plays a vital role in regulating cell survival and death following ischemic injury.Previous studies have shown that pyroptosis is closely related to the activation of the NLRP3 inflammasome in ischemic stroke tissues.This distinctive form of cell death mainly occurs in microglia,neurons,astrocytes and endothelial cells.This paper reviews the role of pyroptosis mediated by inflammasomes in ischemic stroke,discussing the targets and substances that affect the activation of the NLRP3 inflammasome,which can provide a new theoretical and experimental basis for the treatment of ischemic stroke.