Effects of p38 Mitogen-Activated Protein Kinases(p38MAPK) Inhibitor on Acute Lung Injury Induced by Trauma-Hemorrhagic Shock in Rats

Objective:To investigate the effects of p38 MAPK inhibitor on acute lung injury induced by trauma-hemorrhagic shock in rats.Methods:Thirty SPF male rats were randomly assigned into three equal groups(n=10):sham procedure(S)group,acute lung injury model(M)group,acute lung injury model and specific p38 MAPK inhibitor SB203580treatment(SB)group.M and SB groups were established the animal model of acute lung injury.SB group rats were infused with SB203580 for 2mg/kg in 30 min before performing model establishment.The left femoralartey was cannulated to monitor mean arterial pressure and heart rates;At 6hafter trauma,arterial blood was drawn for blood gas analysis.The levels of TNF-α,IL-6and IL-1βin the serum were measured using enzyme-linked immunosorbent assays(ELISA).PMN percentage in bronchoalveolar lavage fluid(BALF)were measured.Lung tissue myeloperoxidase(MPO)activation was determinated by Colorimetric assay.Lung tissue samples were collected to examine pulmonary pathologic changes were observed under light microscopy and electron microscopy.p38 MAPK protein expressions were assessed by Western blot.Results:At 2and 4h,MAP and HR was significantly decreased in T/HS rats(P0.05)versus S group,whereas fluctuation in MAP and HR was relatively stable following the infusion of 2mg/kg SB203580.Compared with group S,pH and PaO2 were significantly decreased;PaCO2,PMN percentage in BALF,MPO activation and TNF-α,IL-6,IL-1βlevels in serum were increased and p38 MAPK expressions were significantly increased in lung tissue(P0.05).Compared with group M,pH and PaO2 were significantly decreased,PMN percentage in BALF,MPO activation and TNF-α,IL-6,IL-1βlevels in serum were decreased and p38 MAPK expressions were significantly decreased in lung tissue(P0.05).Conclusion:p38MAPK inhibitor SB203580 could decrease acute lung injury induced by trauma-hemorrhagic shock in rat through reducing the expression of lung p38 MAPK and the level of serum TNF-α,IL-6,and IL-1β.