Objective      To investigate the expression of p38MAPK in hyperoxic lung injury (HLI)

and explore the protective effect of substance P (SP) on HLI and its mechanism.       Methods      Thirty-two SD rats were divided randomly into 4 groups with 8 rats in each group: a room-air plus saline group

a room-air p

lus SP group

a hyperoxia injury plus saline group

and a hyperoxia injury plus SP group. Rats were injected with SP (1×10

-6

mol·L

-1

·kg

-1

·d

-1

) intraperitoneally in the room-air plus SP group and hyperoxia injury plus SP group. The rats were sacrificed after 7 d of experiment. Lung pathology was examined with light microscopy. Lung wet/dry (W/D) ratio and the content of SP and PCNA in lung were evaluated. The distribution and quantity of p38MAPK protein were detected by immunohistochemistry and Western blotting

respectively.       Results      The pathological changes were observed in the lungs of all the hyperoxia injury groups

while the lung pathological pictures in the hyperoxia injury plus SP group was improved significantly as compared to those in the hyperoxia injury plus saline group. Lung W/D in all the hyperoxia injury groups was significantly higher than that in the room-air plus saline group at day 3 or 7. Lung W/D in the hyperoxia injury and SP group was decreased significantly as compared to that in the hyperoxia injury plus saline group at day 7. The content of SP in the hyperoxia injury and SP group and room-air plus SP group were increased significantly as compared to that in the room-air plus saline group. P38MAPK-positive cells increased in the hyperoxia injury plus saline group as compared to those in the room-air plus saline group. In the hyperoxia injury and SP group

the positive cells remarkably decreased as compared to those of the hyperoxia injury plus saline group. P38MAPK content was higher in the hyperoxia injury plus saline group than in the room-air plus saline group

and p38MAPK expression in the hyperoxia injury plus SP group decreased significantly as compared to that in the hyperoxia injury plus saline group. Changes in W/D ratio and PCNA expression were comparable with those of p38MAPK protein quantity.       Conclusion      Hyperoxia activates p38MAPK signaling pathway. SP may exert a protective effect on HLI through attenuation of

hyperoxia-induced p38MAPK activation.