Role Of P38MAPK In Hyperoxia-induced Lung Injury In New-born Rats

ObjectiveHyperxia refers to the condition in which the oxygen concentration is higher than that in normal air pressure. Hyperxia is important for the rescue of newborn. However, when persistent exposure to hyperxia, much active oxygen will set free, which may lead to acute lung injury (ALI), and then chronic lung injury and bronchopulmonary dysplasia (BPD), which may influence the life quality of newborn. Lung is the major target organ for oxidative stress injury. At present, the pathogenesis of hyperoxia-induced lung injury in newborn is still elusive. Much paper published showed that the quick activation of neutrophil, much release of various kinds of cytokines and the overexpression of TGF-β₁ may take part in important roles during the development and turnover of hyperoxia-induced lung injury. In this research, new-born SD rats was used to establish animal models of hyperoxia-induced lung injury. The expression of p38 mitogen activated protein kinase (p38MAPK) was determined. SB203580 was used as the specific inhibitor of p38MAPK and its effects on treating hyperoxia-induced lung injury will be determined. By observing the change of the concentration of IL-8 and TGF-β₁ before and after treatment with SB203580, the change of p38MAPK expression and its role in hyperoxia-induced lung injury in new-born rats were observed, and at the same time, the protective effect of SB203580 on hyperoxia-induced lung injury in new-born rats was observed.Methods160 new-born rats were randomly assigned to 4 groups: group I. air control group, groupâ…¡. hyperxia group, groupâ…¢. hyperxia + SB203580 group, groupâ…£. hyperxia + physiologic saline group. Groupâ…¡,â…¢andâ…£were exposed to hyperxia (>95% ) for 72 h, at the same time, group I was fed in normal air. SB203580 or physiologic saline was injected intraperitoneally at 5 mg/kg in groupâ…¢or groupâ…£, 1/d, for 3 days. The rats were killed at the time points of 12 h, 24 h, 72 h and 1 week. The lung wet/dry weight ratio (W/D) and lung histophathological changes were examined in all groups, the expression of p38MAPK was determined by Western-blot, and the concentration of IL-8 and TGF-β₁ in lung tissues were examined by ELISA.Resultsâ‘ At 12 h and 24 h, there were no significant differences of lung histophathological changes in all groups. In groupâ…¡and groupâ…£, there were significant acute inflammation and hemorrhage at 72 h and 1 week, widen alveolar septum and indiscriminate tissue structure were found. In groupâ…¢, acute inflammation were also apparent at 72 h and at 1 week, all the inflammatory cells were almost absorbed and the pulmonary alveolus growth and structure were almost normalized.â‘¡Compared to groupâ… , the lung W/D in groupâ…¡showed no difference at 12 h and 24 h. But at 72 h and 1week, the lung W/D in groupâ…¡was significantly higher than that in groupâ… . When compared to groupâ…¢, the lung W/D also displayed no difference at 12 h and 24 h, however, at 72 h and 1 week, the lung W/D in groupâ…£was greatly higher than that in groupâ…¢.â‘¢At 12 h, p38MAPK in hyperoxia-induced lung injury new-born rats began to express, and at 72 h the expression was highest and then began to decrease. At 72 h, there were no expression of p38MAPK in groupâ… , the expression in groupâ…¡could be detected, and the expression in groupâ…£was obviously higher than groupâ…¢.â‘£In groupâ…¡and groupâ…£, the concentration of IL-8 and TGF-β₁ showed time-dependent increase, and at all the time points, the concentration of IL-8 and TGF-β₁ in the 2 groups were all higher than that in groupâ… and groupâ…¢(P < 0.01).Conclusionâ‘ New-born rats may develop to ALI after persistent exposure to hyperxia.â‘¡p38MAPK may take part in an important role during the development of hyperoxia-induced lung injury in new-born rats.â‘¢SB203580 can suppress the expression of IL-8 and TGF-β₁ by blocking the expression of p38MAPK,and then relieve the hyperoxia-induced lung injury in new-born rats.