Cycloxygenase Inhibition Enhances the Effects of Surfactant Therapy in Endotoxin-Induced Rat Model of ARDS

摘要

The present study examines the relationships between inflammation and surfactant protein (SP) expression in a rodent model of acute respiratory distress syndrome (ARDS). Rats were intratracheally instilled with lipopolysaccharide (LPS) for 72 hours to induce ARDS and further treated with exogenous surfactant. Prostaglandin E₂ (PGE₂) levels, cycloxygenase (COX) activity and alterations in SP-A apoprotein were measured. COX and SP-A expressions in lung tissue and SP-A-positive cells were determined by Western blot and immunofluorescence, respectively. PGE₂ levels and COX activity and its expression were increased with LPS exposure, whereas SP-A protein and percentage of SP-A-positive cells were decreased, which were subsequently reverted back by exogenous surfactant instillation. Because inhibition of COX-2 action is proposed to be useful in various inflammatory lung injuries, these results suggest that COX-2 expression and the possible beneficial effects of its inhibition on lung inflammation and dysfunction with LPS-ARDS corresponds closely with reduced SP-A expression.