ObjectiveTo investigate the effect of Gasdermin D(GSDMD) gene knockout on lung injury and reactive oxygen species (ROS)/nod-like receptor protein 3 (NLRP3)/cysteinyl aspartate specific proteinase-1(caspase-1) pyroptosis pathway of pneumonia mice. Methods20 wild-type (WT) male C57BL/6J mice were randomly divided into WT control group and WT model group. 20 GSDMD gene knockout (KO) mice were randomly divided into KO control group and KO model group, each group consisted of 10 animals. The pneumonia model was induced by puncturing the nasal mucosa with a sterile needle and slowly instilling Streptococcus pneumoniae suspension in WT model group and KO model group. Serum and bronchoalveolar lavage fluid (BALF) were collected 7 days after modeling, and the levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected; the lung tissues were collected and the dry wet ratio (W/D), pathological changes, the levels of malondialdehyde (MDA), total antioxidant capacity (T-AOC), superoxide dismutase (SOD), ROS activity, and the protein expression levels of GSDMD, GSDMD-N, NLRP3, Caspase-1 were detected. ResultsThe lung tissue of WT model group showed cell infiltration with alveolar septal thickening, the ratio of W/d in lung tissue, the levels of IL-1β, IL-6 and TNF-α in serum and BALF, the levels of MDA, ROS, NLRP3 and Caspase-1 in lung tissue were all higher than those in WT control group, the levels of T-AOC and SOD in lung tissue were lower than those in WT control group (P<0.05), and the levels of serum, BALF and lung tissue in KO control group were not significantly different from those in WT control group (P>0.05) There was no expression of GSDMD-N in the lung tissue of KO model group, lung tissue w/d ratio, serum and BALF levels of IL-1β, IL-6, TNF-α, MDA, ROS activity, GSDMD-N, NLRP3 and Caspase-1 protein expression were lower than those in WT model group, the levels of T-AOC and SOD in lung tissue were higher than those in WT Model Group (P<0.05). ConclusionGSDMD gene knockout attenuates lung injury and inhibits ROS/NLRP3/Caspase-1 pathway in pneumonia mice.