NLRP3炎性体与2019冠状病毒病(COVID-19)肺损伤的研究进展

Progress in the relationship between NLRP3 inflammasome and lung injury in COVID-19

强烈的炎症反应是2019冠状病毒病(COVID-19)急性肺损伤的主要原因,严重急性呼吸综合征冠状病毒2(SARS-CoV-2)通过与受体血管紧张素转化酶2(ACE2)结合进入肺部上皮细胞等靶细胞,激活含pyrin结构域核苷酸结合寡聚结构域样受体家族蛋白3(NLRP3)炎性体,活化前体caspase-1,释放成熟的IL-1β和IL-18等炎性细胞因子,参与炎症反应及诱导细胞焦亡,从而导致COVID-19患者肺部炎症细胞浸润,充血,水肿,严重者可伴有急性呼吸窘迫综合征(ARDS)、弥散性血管内凝血(DIC)等多种并发症。目前尚无治疗COVID-19的特定药物,MCC950及秋水仙碱等NLRP3炎性体抑制已经广泛应用于治疗各种炎症性疾病,而目前这些药物也正处于治疗COVID-19患者的临床试验阶段。我们总结了COVID-19发病机制及SARS-CoV激活NLRP3炎性体途径,以期初步揭示NLRP3炎性体在SARS-CoV-2感染过程中所扮演的角色及其机制,为研发相关靶向药物提供理论基础。

Severe inflammatory responses are considered responsible for acute lung damage in COVID-19.SARS-CoV-2 enters lung cells via ACE2,and the NLR family pyrin domain containing 3(NLRP3)inflammasome and the pro-caspase-1 are then activated,followed by release of mature IL-1βand IL-18 and other inflammatory cytokines,thereby leading to inflammation and apoptosis.This inflammatory process induces syndromes such as inflammatory cell infiltration,congestion,and edema in the lungs of COVID-19 patients.Some severe cases reported complications including acute respiratory distress syndrome(ARDS)and diffuse intravascular coagulation(DIC).There is no specific drug available for the treatment of COVID-19 at present.MCC950,colchicine and other NLRP3 inflammasome inhibitors,have been widely used in the treatment of various inflammatory diseases,and are currently in clinical trials for the treatment of COVID-19 patients.Here we reviewed the pathogenesis of COVID-19 and the SARS-CoV activation pathway of NLRP3 inflammasome,in order to reveal the role and mechanism of NLRP3 inflammasome in the process of SARS-CoV-2 infection,and provide a theoretical basis for the development of related targeted drugs.