摘要
Background A proinflammatory milieu emerging in the lung due to neutrophil accumulation and activation is a key in the pathogenesis of acute lung injury （ALI）.15-deoxy-△12,14-prostaglandin J2 （15d-PGJ2）,one of the terminal products of the cyclooxygenase-2 pathway,is known to be the endogenous ligand of peroxisome proliferator-activated receptor y （PPAR-y） with multiple physiological properties.Growing evidence indicates that 15d-PGJ2 has anti-inflammatory,antiproliferative,cytoprotective and pro-resolving effects.We investigated whether 15d-PGJ2 has a protective effect against endotoxin-induced acute lung injury in rats.Methods Twenty-four male Wistar rats were randomly assigned into four groups （n=6 per group）：sham＋vehicle group,sham＋15d-PGJ2 group,LPS＋vehicle group,and LPS＋15d-PGJ2 group.The rats were given either lipopolysaccharide （LPS,6 mg/kg intravenously） or saline,and pretreated with 15d-PGJ2 （0.3 mg/kg intravenously） or its vehicle （dimethyl sulphoxide） 30 minutes before LPS.Histological alterations,wet/dry weight （W/D） ratio and myeloperoxidase （MPO） activity as well as tumor necrosis factor （TNF）-α and cytokine-induced neutrophil chemoattractant-1 （CINC-1） levels were determined in lung tissues four hours after LPS injection.Immunohistochemical analysis for intercellular adhesion molecule-1 （ICAM-1） expression and Western blotting analysis for nuclear factor （NF）-κB p65 translocation and IκBα protein levels were also studied.Results 15d-PGJ2 pretreatment significantly attenuated LPS-induced lung injury,and reduced the increased W/D ratio,MPO activity,TNF-α,CINC-1 levels,and ICAM-1 expression in the lung.15d-PGJ2 also suppressed the nuclear NF-ΚB p65 translocation and increased cytosolic IKBα levels.Conclusions 15d-PGJ2 protects against endotoxin-induced acute lung injury,most likely through the reduction of proinflammatory protein levels during endotoxemia subsequent to the inhibition of NF-ΚB activation.
Background A proinflammatory milieu emerging in the lung due to neutrophil accumulation and activation is a key in the pathogenesis of acute lung injury （ALI）.15-deoxy-△12,14-prostaglandin J2 （15d-PGJ2）,one of the terminal products of the cyclooxygenase-2 pathway,is known to be the endogenous ligand of peroxisome proliferator-activated receptor y （PPAR-y） with multiple physiological properties.Growing evidence indicates that 15d-PGJ2 has anti-inflammatory,antiproliferative,cytoprotective and pro-resolving effects.We investigated whether 15d-PGJ2 has a protective effect against endotoxin-induced acute lung injury in rats.Methods Twenty-four male Wistar rats were randomly assigned into four groups （n=6 per group）：sham＋vehicle group,sham＋15d-PGJ2 group,LPS＋vehicle group,and LPS＋15d-PGJ2 group.The rats were given either lipopolysaccharide （LPS,6 mg/kg intravenously） or saline,and pretreated with 15d-PGJ2 （0.3 mg/kg intravenously） or its vehicle （dimethyl sulphoxide） 30 minutes before LPS.Histological alterations,wet/dry weight （W/D） ratio and myeloperoxidase （MPO） activity as well as tumor necrosis factor （TNF）-α and cytokine-induced neutrophil chemoattractant-1 （CINC-1） levels were determined in lung tissues four hours after LPS injection.Immunohistochemical analysis for intercellular adhesion molecule-1 （ICAM-1） expression and Western blotting analysis for nuclear factor （NF）-κB p65 translocation and IκBα protein levels were also studied.Results 15d-PGJ2 pretreatment significantly attenuated LPS-induced lung injury,and reduced the increased W/D ratio,MPO activity,TNF-α,CINC-1 levels,and ICAM-1 expression in the lung.15d-PGJ2 also suppressed the nuclear NF-ΚB p65 translocation and increased cytosolic IKBα levels.Conclusions 15d-PGJ2 protects against endotoxin-induced acute lung injury,most likely through the reduction of proinflammatory protein levels during endotoxemia subsequent to the inhibition of NF-ΚB activation.
