Lipoxin A4 alleviates lung injury in sepsis rats through p38/MAPK signaling pathway.

Abstract

The aim of the study was to explore the effect of lipoxin A4 (LXA4) on lung injury in sepsis rats through the p38/mitogen-activated protein kinase (MAPK) signaling pathway. Sprague-Dawley rats were used for the study. The rat model of sepsis-induced acute lung injury was established via cecal ligation (Sepsis group, n=20). LXA4 (0.1 mg/kg) was injected at 6 h after modeling (Treatment group, n=20), and a The Control group (n=20) was also set up. The 7-day survival rate was 100% in The Control group, and LXA4 raised the survival rate of rats in the Sepsis group from 40% to 60% (P<0.01). Alveolar fluid clearance (AFC) significantly declined and the wet/dry weight (W/D) ratio of lung tissues rose remarkably in the Sepsis group compared with those in the Control group, while LXA4 restored AFC and reduced the W/D ratio of lung tissues (P<0.05), suggesting that LXA4 treatment reduces lung fluids and partially enhances AFC, thus lowering the W/D ratio of lung. The total cell count, polymorphonuclear neutrophils (PMN) percentage and concentration of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 in bronchoalveolar lavage fluid (BALF) were obviously increased in the Sepsis group compared with those in the Control group, while they were markedly decreased in the Treatment group (P<0.05). The activity of myeloperoxidase (MPO) in lung tissue homogenate was evidently higher in the Sepsis group than that in The Control group, while it was notably lower in the Treatment group than that in the Sepsis group after LXA4 treatment (P<0.05). Moreover, it was observed microscopically that the morphology of lung tissues was intact in the Control group. Finally, the results of Western blotting manifested that the p-p38/ MAPK protein expression was remarkably increased in the Sepsis group, indicating the activation of the p38/MAPK pathway, while it was remarkably decreased in the Treatment group, indicating the inhibited activity of the pathway (P<0.05). LXA4 has an anti-inflammatory effect on sepsis rats with lung injury, and such effect is related to the p38/MAPK signaling pathway.