Role of p38MAPK signaling pathway in up-regulation of heme oxygenase-1 expression during hemorrhagic shock and resuscitation-induced acute lung injury in mice

Abstract

Objective To evaluate the role of p38MAPK signaling pathway in the up-regulation of heme oxygenase-1 （HO-1） expression during hemorrhagic shock and resuscitation （HSR）-induced acute lung injury （ALI） in mice. Methods Thirty-two C3H/HeN （wild-type） mice, aged 10-12 weeks, weighing 20-25 g, were randomly divided into 4 groups （n = 8 each）： sham operation group （group S）; group HSR; FR167653 （a p38MAPK inhibitor） group （group FR） and FR167653 ＋ HSR group （group FR ＋ HSR）. HSR was induced according to the methods described by Ayala et al. MAP was reduced to 35-45 mm Hg and maintained for 60 min.Then the animals were resuscitated with transfusion of the shed blood and lactated Ringer＇s solution equivalent to the volume of shed blood. FR167653 5 mg/kg was injected intravenosly in group FR. FR167653 5 mg/kg was injected intravenously 30 min before blood-letting in group FR ＋ HSR. The animals were sacrificed by exsanguination at 6 h after resuscitation. The lungs were immediately removed for microscopic examination. The W/D lung weight ratio was calculated and the levels of myeloperoxidase （MPO）, IL-10, IL-6 and HO-1 and activated p38MAPK were determined （by ELISA）.Results Compared with group S, the pathological score, W/D ratio, the levels of MPO, IL-10, IL-6 and HO-1 and the level of activated p38MAPK were significantly increased in group HSR, the pathological score, W/D ratio and the level of HO-1 were significantly increased in group HSR ＋ FR （ P 〈 0.01） .Compared with group HSR, the pathological score, W/D ratio, the levels of MPO, IL-10, IL-6 and HO-1 and activated p38MAPK were significantly decreased in group HSR ＋ FR （ P 〈 0.01 ）. Conclusion p38MAPK signaling pathway mediates the up-regulation of HO-1 expression during HSR-induced ALI in mice. Key words: p38 Mitogen-activated protein kinases; Heme oxygenase-1; Shock, hemorrhagic; Respiratory distress syndrome, adult