Agmatine suppresses the imidazoline I2 receptor/ribosomal S6 kinase 2/NF-κB signaling pathway regulating alveolar macrophage polarization and ameliorating sepsis-associated acute lung injury.

Abstract

Acute respiratory distress syndrome (ARDS) is an acute diffuse inflammatory lung injury characterized by damage to alveolar epithelial cells and pulmonary capillary endothelial cells. Compared with ARDS caused by other causes, the subtypes of ARDS caused by sepsis are more serious and lead to poor prognosis and higher mortality. Agmatine (AGM) is a biological metabolite of L-arginine decarboxylation, proven to ameliorate sepsis-induced acute lung injury (SALI), but the mechanism remains unclear. Therefore, this study aims to explore the role of AGM in SALI, clarify the relationship between the I₂R/RSK2/NF-κB signaling pathway regulated by AGM and macrophage polarization, and provide a theoretical basis for the clinical treatment of SALI. Cellular and animal models of lung injury in sepsis were established with lipopolysaccharide (LPS). We conducted a series of experiments to examine the oxygenation index (OI), wet/dry ratio (W/D) of the lung, pathological changes, levels of inflammation, Apoptosis and related protein expression in different groups of mice. Finally, we found that AGM can ameliorate sepsis-induced acute lung injury by suppressing the I₂R/RSK2/NF-κB signaling pathway and modulating polarization of alveolar macrophage.