Investigation Into The Mechanism By Which Dexmedetomidine Attenutates Acute Lung Injury Based On Bioinformatics

BackgroundAcute lung injury(ALI)/acute respiratory distress syndrome(ARDS)is a kind of alveolar capillary barrier injury caused by various pathogenic factors,which leads to diffuse p ? lmonary interstitial and alveolar edema and acute hypoxic respiratory insufficiency.However,the high morbidity and mortality of ARDS suggest that the pathogenesis of ARDS is not clear.Bioinformatics can effectively obtain some disease-related target genes and signal pathways by analyzing the data detected by high-throughput methods such as chips.Dexmedetomidine,as a commonly used clinical adjuvant,can play a role in anti-inflammation and improving lung function.Therefore,the purpose of this study is to explore mechanism underlying dexmedetomidine reducing LPS-induced acute lung injury using bioinformatics analysis combined with animal experimental methods.Material and method1.The microarray data were downloaded from the GEO public database,and the co-expressed differentially expressed genes related to acute lung injury were screened by R language software,and then the gene function and signal pathway enrichment were analyzed by David database.In addition,the protein-protein interaction network was analyzed by string database,and then the key differentially expressed genes were screened by Cytoscape software.2.Establish an acute lung injury model induced by lipopolysaccharide(LPS).Polymerase chain reaction(PCR)was used to detect the expression levels of key differentially expressed genes in lung tissue of mice.3.C57BL/6 mice were randomly divided into four groups:normal control group,sepsis group,sepsis group+dexmedetomidine group and sepsis group+dexmedetomidine+yuxiangbin group.Each group was pretreated with normal saline or drugs before acute lung injury.After the establishment of the ALI model,the concentration of protein and inflammatory factors in the Bronchoalveolar lavage fluid(BALF)were detected,and the exudation of inflammatory cells was observed by Giemsa staining.The ratio of wet to dry weight of lung tissue was measured,HE staining was performed and the acute lung injury was scored.Finally,PCR and WB were used to detect the expression of the target genes in the lung tissue of mice.Res ? lt1.71 Co-DEGs had been screened.2.Co-DEGs were mainly enriched in toll like receptor and NF-?B signaling pathways.3.The protein concentration of BALF,the ratio of wet to dry weight of lung tissue and the score of acute lung injury in LPS group were significantly higher than those in the control group.4.The res P Its of Giemsa staining showed that the exudation of inflammatory cells in LPS group was significantly higher than that in the control group;HE staining showed that the lung tissue structure of LPS group was seriously damaged.5.The res ? Its of PCR showed that the relative expression values of Il6,Il1b,Ccl2,Cxcl2,Tlr2,Icam1,Csf2 and Ccl4 in LPS group were significantly higher than those in the control group.6.Dexmedetomidine significantly reduced the exudation of inflammatory cells,protein concentration and inflammatory factors concentration in the alveolar lavage fluid of LPS induced ALI,and significantly reduced the wet dry weight ratio and acute lung injury score in the lung tissue of LPS induced ALI.7.Dexmedetomidine reduces Tlr2 mediated NF-?B signal pathway genes and protein expression in LPS induced ALI.Conclusion1.Bioinformatics analysis can effectively screen genes and signal pathways related to acute lung injury2.Tlr2 is a key gene in acute lung injury.3.Toll like receptor and NF-?B signaling pathways are important in the development of acute lung injury.4.Dexmedetomidine can reduce LPS induced acute lung injury by inhibiting Tlr2 mediated NF-?B signaling pathway...