Objective    To investigate the effect of ethyl pyruvate (EP) on pulmonary high mobility group box-1 protein (HMGB1) expression and acute lung injury in rats with delayed resuscitation after burn injury.     Methods    Wistar rats were inflicted to 30% full-thickness scald injury followed with delayed resuscitation. Seventy-eight male rats were randomly divided into sham scald group (n=18)

scald group (n=30)

and EP treatment group (n=30)

and they were sacrificed at 8

24

and 72 h after scald injury. Lung tissue samples were collected to determine HMGB1 mRNA as well as protein expressions

and pulmonary myeloperoxidase (MPO) activity. HMGB1 mRNA level was semi-quantitatively measured by the reverse transcription polymerase chain reaction (RT-PCR) taking GAPDH as an internal standard

and protein expression of HMGB1 was detected by Western blotting and immunohistochemistry. The pathological changes of lung tissues were observed with light microscopy after HE staining.     Results    Compared to sham scald controls

both mRNA and protein expressions of HMGB1 were significantly enhanced in the lung at 8 to 72 h after scald injury (P0.05 or 0.01)

meanwhile pulmonary MPO activities were markedly increased at 8 and 24 h after scald (P0.01). In addition

many inflammatory cells in pulmonary tissues were observed under light microscope following injury. Treatment with EP markedly down-regulated pulmonary HMGB1 mRNA and protein expressions at 8 to 72 h (P0.05 or 0.01)

and reduced pulmonary MPO activities at 8 and 24 h following scald injury (P0.01). The histological morphology of pulmonary lesions was ameliorated after treatment with EP.     Conclusion    These results suggest that HMGB1 might act as a late mediator in the pathogenesis of postburn acute lung injury. Treatment with EP could obviously inhibit pulmonary HMGB1 expression and reduce MPO activity

thereby prevent the development of acute lung injury induced by major burns with delayed resuscitation.