Acute respiratory distress syndrome (ARDS) is a critical condition with high mortality. HMGB1 (high-mobility group protein B1) is one of the key proinflammatory factors in the ARDS “inflammatory storm.” According to previous studies, some microRNAs (miRNAs) play important roles in this process. We aimed to determine the contributing miRNAs targeting the expression and release of HMGB1. miRNA expression in the peripheral blood of patients with ARDS was measured by miRNA microarray. miRNAs targeting HMGB1 were screened and explored for further study. In LPS-induced cell and mouse ARDS models, we explored the effect of this miRNA on the expression and secretion of HMGB1 by Western blot, real-time qPCR, and ELISA. The effects of this miRNA on the NF-κB signaling pathway, proinflammatory cytokines, and NLRP3 (nod-like receptor protein 3) inflammasome were detected by Western blot and real-time qPCR. In ARDS models, microRNA-574-5p (miR-574-5p) expression could be induced by the TLR4/NF-κB pathway upon LPS stimulation. It could suppress the inflammatory response by targeting HMGB1. Enforcing the expression of miR-574-5p or HMGB1 siRNA silencing inhibits the activation of NF-κB signaling pathway and the NLRP3 inflammasome. Moreover, overexpression of HMGB1 reversed the antiinflammatory effect of miR-574-5p. In ARDS mice, overexpression of miR-574-5p suppresses alveolar leukocytes infiltration, interstitial edema, protein effusion, and inflammation. This study demonstrated that miR-574-5p provided negative feedback to LPS-induced inflammation and relieved ARDS. It may provide new therapeutic strategies for ARDS.

急性呼吸窘迫综合征（ARDS）是一种高死亡率的危重病。HMGB1（高迁移率族蛋白B1）是ARDS“炎症风暴”中的关键促炎因子之一。根据以前的研究，一些microRNA（miRNA）在此过程中起重要作用。我们旨在确定靶向HMGB1表达和释放的miRNA。用miRNA芯片检测ARDS患者外周血中的miRNA表达。筛选靶向HMGB1的miRNA，并进行进一步研究。在LPS诱导的细胞和小鼠ARDS模型中，我们通过蛋白质印迹，实时qPCR和ELISA探索了该miRNA对HMGB1表达和分泌的影响。该miRNA对NF-κB信号传导途径，促炎细胞因子，Western blot和实时定量PCR检测NLRP3（nod样受体蛋白3）炎性小体。在ARDS模型中，LPS刺激后，TLR4 /NF-κB途径可诱导microRNA-574-5p（miR-574-5p）表达。它可以通过靶向HMGB1抑制炎症反应。增强miR-574-5p或HMGB1 siRNA的表达可抑制NF-κB信号通路和NLRP3炎性体的激活。此外，HMGB1的过表达逆转了miR-574-5p的抗炎作用。在ARDS小鼠中，miR-574-5p的过度表达可抑制肺泡白细胞浸润，间质性水肿，蛋白质渗出和炎症。这项研究表明，miR-574-5p为LPS诱导的炎症提供了负反馈，减轻了ARDS。它可能为ARDS提供新的治疗策略。