Effect Of P38 MAP Kinase Signaling Pathway On Hyperoxia-Induced Lung Injury

Objective Oxygen therapy is widely used for patients to improve blood oxygen saturation and reduce tissue hypoxia. However,supplemental O2 of prolonged high concentration administered to patients may result in oxidative stress lung injury. The mechanism of hyperoxia-induced lung injury is still unclear . It was suggested that apoptosis was one of the function factors in process of hyperoxia-induced lung injury. P38 MAP kinase, one of the sub-family of mitogen activated protein kinase (MAPK), was considered to be related with cell proliferation, survival and apoptosis. The aim of this study was: 1) to investigate the apoptosis and the p38 MAPK expression in hyperoxia-induced lung injury animal model. 2)to explore the effect of p38 MAPK on apoptosis.Methods Fourty Wistar rats aged three weeks old were randomly divided into room-air control group, hyperoxia groups (hyperoxia-exposure for 1,2,3days), and p38 MAPK inhibition group. The apoptosis index was evaluated by TUNEL technique and the location and quantity of p38 MAPK in lung were detected by immunohistochemistry and Western blot analysis respectively. In some groups, cell apoptosis index and expression of p-p38MAPK were detected after pretreatment with SB203580 .Results Compared with the control group, the lungs of 1,2-day-hyperoxia-exposure group were found no difference. However, the lungs of 3-day-hyperoxia-exposure group showed edema, hemorrhage and inflammatory infiltration. The apoptosis index of 1,2-day-hyperoxia-expose group showed no morphological changes when compared with control group (P>0.05). The number of TUNEL positive cell in the lungs of 3-day-hyperoxia-exposure group significantly increased and the apoptosis index between 3-day-hyperoxia-exposure group and control group was distinctive (P<0.05). Although there were rare p38MAPK positive cell scattered in alveolar and airway epithelial cells in room-air group, the positive p38MAPK cells increased strikingly in hyperoxia injury groups than those in the control group, and many kinds of cells were involved in this process , including alveolar , airway epithelial cells, pulmonary vascular endothelium cells, infiltrative inflammatory cells. Activted p38 MAPK localized to the nucleus and cytoplasm. The Western blot analysis result showed that p-p38 MAPK increased 1 day after hyperoxia, peaked at the 2nd(P<0.05)and decreased at the 3rd. Comparing to those of group with high oxygen treatment, the expression of p-p38MAPK in the inhibition group was weaker and apoptosis index was decreased (P<0.05). ConclusionIn the course of hyperoxia-induced lung injury , cell apoptosis could be induced by high oxygen concentration treatment.The activity of p38 MAPK could be detected in the early stage of high oxygen concentration treatment and the activted p38 MAPK was found in alveolar , airway epithelial cells, pulmonary vascular endothelium cells, infiltrative inflammatory cells.p38MAPK signaling pathway plays a role in the regulation of apoptosis and may be proapoptosis in the course of hyperoxia-induced lung injury.