Protective effect of N-acetylcysteine on hyperoxic lung injury and its relation with p38 mitogen-activated protein kinase signaling pathway

Abstract

To investigate the expression of p38 mitogen-activated protein kinase (MAPK) in hyperoxic lung injury (HLI), and explore the protective effect of N-acetylcysteine (NAC) on HLI and its mechanism. Thirty Wistar rats aged 3 weeks old were divided into five groups with 6 rats in each group according to random digits table: room-air group (A), hyperoxia injury group (B), hyperoxia+NAC group (C), hyperoxia+p38 MAPK inhibitor (SB203580) group (D), hyperoxia+NAC+SB203580 group (E). Rats in NAC groups were injected with NAC (200 mg/kg) intraperitoneally, and they received an intravenous injection of SB203580 (0.5 mg/kg) in SB203580 groups. The animals were sacrificed after 7 days of experiment. Lung pathology and grade of lung tissue injury were examined with light microscopy, lung wet/dry (W/D) ratio, total protein (TP) level in bronchoalveolar lavage fluid (BALF) and permeability coefficient were evaluated. The location and quantity of phosphorylation p38 MAPK (p-p38 MAPK) protein were detected by immunohistochemistry and Western blotting analysis respectively. The pathological changes in the lung in B group included severe alveolar oedema with inflammatory cells aggregation and red blood cell leakage, while the lung pathological pictures in C, D, E groups were improved significantly compared with B group. p-p38 MAPK positive cells increased in B group compared with those in A group, involving many types of pulmonary cells, especially in infiltrating inflammatory cells. In C, D, E groups, the positive cells remarkably decreased compared with B group. p-p38 MAPK content was higher in B group than that in A group (0.20+/-0.03 vs. 0.11+/-0.01, P<0.05), and p-p38 MAPK expressions in C, D, E groups decreased significantly compared with B group (0.16+/-0.02, 0.15+/-0.01, 0.14+/-0.02 vs. 0.20+/-0.03, all P<0.05), but were higher than those in A group (all P<0.05). There was no significant difference in p-p38 MAPK quantity among three groups. Changes in W/D ratio, TP and permeability coefficient among groups were comparable with those of p-p38 MAPK protein quantity. Reactive oxygen species (ROS) activated p38 MAPK signaling pathway. NAC may exert a protective effect on HLI through attenuation of hyperoxia-induced p38 MAPK activation.