Mechanism Of Glucocorticoid Mediates ALI/ARDS Via NLRP3 Inflammasome Signaling Pathway

Objective:Presently, the incidence and mortality of ALI/ARDS in ICU is very high, and the application of glucocorticoids in ALI/ARDS is controversial. The purpose of this study is to explore the mechanism of the role of glucocorticoids in ALI/ARDS. Methods: To detect related protein expression of NLRP3 inflammatory signaling pathways by Western Blot and relative expression of mRNA by Q-PCR in vitro experiment. Establish animal model of ALI, to explore the effect of dexamethasone and NLRP3 inflammatory in ALI/ARDS.Results: Vitro experiments show that dexamethasone inhibits NLRP3 inflammasome activation via inhibition the NF-k B signaling pathway and suppresses the activation downstream of NLRP3 inflammasome by inhibiting the production of mitochondrial ROS. Animal experiment results show that dexamethasone can significantly reduce the recruitment of alveolar neutrophils, the secretion of inflammatory factors, ease the extent of lung injury, while the inflammatory response of NLRP3-/- mice are significantly reduced, and the degree of lung injury is mild.Conclusion: In conclusion, glucocorticoid can inhibit the NLRP3 inflammasome signaling pathway activation by acting on NF KB signaling pathway or can inhibit caspase-1 mature and IL-1βand IL-18 secretion by inhibiting mitochondrial ROS to reduce damage, improve symptoms.