Agomir-223 treatment after lung blast injury reduces the inflammatory response by regulating the NLRP3 inflammasome to inhibit M1 macrophage function

Blast lung injury (BLI) is a significant cause of death in military conflicts and terrorist attacks. At present, the specific pathogenesis is not clear, and clinical treatment still relies mainly on symptomatic support. In this study, we aimed to explore the mechanisms of MicroRNAs in shock wave-induced lung blast injury. C57BL/6 adult male mice were exposed to either a sham or blast delivered via a shock tube. The time point at which lung tissue injury was the most severe was selected, and the differentially expressed miRNA agomiR-223 was screened through whole-transcriptome RNA Sequencing. After treatment with agomiR-223, pathological changes in the lung tissue and the expression levels of NLRP3, ASC, Caspase-1, IL-1β, and IL-18 were compared. The infiltration of macrophages and the expression of the M1 phenotype markers iNOS and CD86 and the M2 phenotype marker Arg-1 were also measured to evaluate the effect of miR-223 in the treatment of lung blast injury. The most severe lung injury occurred 6 h after the explosion, with significantly downregulated expression of miR-223 and upregulated expression of the downstream target NLRP3 inflammasome, which recruited and transformed macrophages into the M1 phenotype. Nasal administration of AgomiR-223 significantly inhibited the inflammatory response of lung tissue in BLI mice, reduced lung tissue damage, and improved the survival rate.

Inflammatory reaction; Lung blast injury; Macrophage phenotype; NLRP3 inflammasome; miR-223.