The Molecular Mechanisms of Imatinib Treatment on Acute Lung Injury in Septic Mice Through Proteomic Technology.

Acute lung injury (ALI) is the most common complication of sepsis. Despite considerable progress in the treatment of sepsis, the effective treatment strategies are lacking. A previous study has shown that imatinib reduces the rate of acute pulmonary damage in septic mice; however, the molecular mechanism remains unclear. Therefore, the current study aimed to investigate the potential mechanism by which imatinib alleviates ALI in septic mice. A septicemia model was established by intraperitoneal injection of lipopolysaccharide (LPS), followed by tail vein injection of imatinib in the treatment group. Enzyme-linked immunosorbent assay (ELISA) was used to detect inflammatory factors, and hematoxylin staining was used to detect pathological injury to the lung tissue. Tandem mass tag (TMT) quantitative labeling technology was used for proteomic sequencing analysis. The main target protein was identified through bioinformatics, and its expression was confirmed using western blotting. We identified 128 differentially expressed proteins were associated with the protective effects of imatinib against septic lung injury. Functional enrichment analysis indicated that these proteins may be related to electron transfer, coagulation, and endothelial cell regulation in the oxidative respiratory chain. Enrichment of the nuclear factor-kappa B (NF-kB) signaling pathway, complement-coagulation cascade, and chemokine signaling pathway was also observed. Additionally, we found that the expression of CCAAT/enhancer-binding protein delta (CEBPD) and pyruvate dehydrogenase kinase 4 (PDK4) increased in the sepsis group but decreased in the imatinib group. Imatinib may reduce ALI in mice with sepsis by participating in oxidative respiratory and inflammatory responses, clotting response-related signaling pathways, and downregulating CEBPD and PDK4 expression.