Intervention Study Of Sivelestat On The Inflammatory Response Of Lung Tissue In Mice With Acute Lung Injury

Background:Acute lung injury(ALI)or acute respiratory distress syndrome(ARDS)is a familiar disease with high mortality and no specific treatment in the clinical.will accelerate the progression of ALI/ARDS,and NLRP3 inflammasome is a major participant in the occurrence of inflammatory response.NLRP3 inflammasomes include NLRP3,ASC and CASPASE-1.The activation of NLRP3 inflammasomes promotes the maturation and release of downstream inflammatory cytokines IL-18and IL-1?,and induces cell pyroptosis,thus triggering a series of inflammatory responses.As a neutrophilic elastase inhibitor,siverelostat competitively inhibits neutrophilic activation and reduces neutrophilic infiltration during acute respiratory distress syndrome,thereby providing lung protection^[1].Objective:In this study,the changes of NLRP3,CASPASE-1 and IL-18 in lung tissues of mice with acute lung injury were studied by replicating acute lung injury mouse model,and the effects of sivelestat on the expression of NE,p-NF-?B,NLRP3,IL-1?and IL-18 protein in lung tissues of mice with acute lung injury were investigated.Methods:A mouse model of acute lung injury was established in vivo.C57BL/6male mice were randomly divided into 4 groups with 8 mice in each group:normal control group(CON),model group(LPS),Model+sivelestat group(LPS+SV),Model+NLRP3 inflammasome inhibitor group(LPS+OLT).The acute lung injury model was induced by intraperitoneal injection of Lipopolysaccharide(LPS),and the acute attack manifestations of each group were observed.The enzym-linked immunosorbent assay(ELISA)was used to determine the expression levels of IL-1?in lung tissues of mice,and the protein expressions of NLRP3,p-NF-?B,Caspase-1,IL-1?,IL-18 and NE were detected by Western blot.The inflammatory infiltration of lung tissue of mice was observed by HE staining.Results:The wet-to-dry ratio of lung was significantly increased in mice with LPS induced acute lung injury.There were obvious inflammatory infiltrates in lung tissue.The expression of NLRP3,p-NF-?B,CASPASE-1,IL-1?,IL-18,NE and other proteins increased.The sivelestat pretreatment group and the inflammasome inhibitor group decreased the wet-to-dry ratio,improved the inflammatory infiltration,and down-regulated the expression of NE,p-NF-?B,NLRP3,CASPASE-1,and IL-18.In addition,the inflammasome inhibitor group decreased the expression of IL-1?protein.Conclusion:Sivelestat not only attenuates LPS-induced acute lung injury by inhibiting neutrophil elastase,but also attenuates inflammation induced by acute lung injury by partially inhibiting the activation of NLRP3 inflammasome.