缺血性卒中线粒体焦亡机制相关研究进展  

Research progress on mitochondrial pyroptosis mechanism in ischemic stroke

作　　者：蔡珂 王钦鹏[1] 魏阳阳 李婷婷 王国娟[1] 梁成[1] CAI Ke;WANG Qinpeng;WEI Yangyang;LI Tingting;WANG Guojuan;LIANG Cheng(Department of Neurology ICU,Lanzhou University Second Hospital,Lanzhou,Gansu 730030,China)

机构地区：[1]兰州大学第二医院神经内科ICU,甘肃兰州730030

出　　处：《中华全科医学》2024年第5期850-854,共5页Chinese Journal of General Practice

基　　金：甘肃省自然科学基金项目(21JR11RA129)。

摘　　要：缺血性卒中作为最常见的脑血管疾病,具有高发病率、高死亡率、高致残率、高复发率的特点,给患者、家庭及社会带来沉重的负担,其治疗的主要目的是及时开通血管恢复灌注、挽救缺血半暗带、改善神经功能。关于缺血性卒中的病理生理学机制以及其治疗的相关研究始终是一大热点,现已有大量研究表明,神经炎症是缺血性卒中的一个重要机制。细胞焦亡作为一种细胞的炎性死亡方式,与多种疾病及损伤机制密切相关,包括缺血性卒中的发生发展过程;细胞焦亡过程中有炎性小体、caspase-1、GSDMD等多种关键蛋白,而其中GSDMD作为细胞焦亡的执行蛋白,可在细胞膜上打孔,使得IL-1β、IL-18等炎性因子释放至胞外产生炎症反应;最新研究发现GSDMD不仅可在细胞膜上打孔,也可通过打孔破坏线粒体膜,导致线粒体功能受损、内容物释放,且线粒体膜受损先于细胞膜受损,既使得细胞焦亡过程被扩大,也可诱导其他途径的细胞死亡;因此抑制GSDMD的打孔功能、通过线粒体移植改善缺血细胞线粒体功能可有效抑制炎症反应,改善缺血半暗带功能,从而起到神经保护作用。本文简要介绍细胞焦亡的过程及GSDMD在焦亡过程中打孔的作用机制,重点阐述线粒体焦亡过程及其在缺血性卒中的相关研究进展,并为缺血性卒中的治疗找寻新的思路。As the most common cerebrovascular disease,ischemic stroke has the characteristics of high incidence,high mortality,high disability rate,and high recurrence rate,which brings a heavy burden to patients,families,and society.The main purpose of its treatment is to timely open blood vessels to restore perfusion,rescue ischemic penumbra,and improve neurological function.Research on the pathophysiological mechanism and treatment of ischemic stroke has always been a hot spot.A large number of studies have shown that neuroinflammation is an important mechanism of ischemic stroke.As an inflammatory cell death mode,pyroptosis is closely related to a variety of diseases and injury mechanisms,including the occurrence and development of ischemic stroke.There are a variety of key proteins in the process of pyroptosis,such as inflammasome,caspase-1,and Gasdermin D(GSDMD).GSDMD,as the executive protein of pyroptosis,can punch holes in the cell membrane,causing inflammatory factors such as IL-1βand IL-18 to be released into the extracellular space to produce an inflammatory response.Recent studies have found that GSDMD can not only punch holes in the cell membrane but also destroy the mitochondrial membrane by punching holes,leading to impaired mitochondrial function and release of mitochondrial content.The mitochondrial membrane damage occurs before the cell membrane damage,which not only expands the pyroptosis process but also induces cell death through other pathways.Therefore,inhibiting the perforating function of GSDMD and improving the mitochondrial function of ischemic cells through mitochondrial transplantation can effectively inhibit the inflammatory response and improve the function of the ischemic penumbra,thus playing a neuroprotective role.In this review,we briefly introduce the process of pyroptosis and the mechanism of GSDMD drilling in the process of pyroptosis,focusing on the process of mitochondrial pyroptosis and its related research progress in ischemic stroke,and looking for new ideas for the treatment of i

关 键 词：细胞焦亡 成孔蛋白D 线粒体 缺血性卒中 

分 类 号：R743.33[医药卫生—神经病学与精神病学]