Role of p38 MAPK in ischemia/reperfusion-induced gastric injury in mice

Abstract

Objective To investigate the role of p38 MAPK on gastric ischemia/reperfusion(I/R)-induced injury in mice.Methods C57BL/6 mice were randomly divided into three groups:sham+vehicle group,I/R+vehicle group(as control),and I/R+CNI-1493 group.The gastric I-R injury mice were prepared by occluding the celiac artery for 30 min followed by reperfusion for 1 h.Sham-operated animals underwent the same surgical procedure without clamping.Physiological saline(0.9% NaCl,10 ml/kg) or CNI-1493(a p38 MAPK inhibitor,10 ml/kg,2 mg/ml) was intraperitoneally administered 1 h before ischemia.A picture of the whole stomach was obtained after fixation with formalin,and the bleeding area in the whole stomach was obtained by a digital imaging analyzer(Image J 1.4.NIH).The levels of phospho-and total-mitogen-activated protein kinases(MAPKs including p38,JNK,and ERK),phospho-nuclear factor-κB(NF-κB) and cleaved Caspase-3 in the injured stomach tissue were determined by Western blotting analysis.Results Compared with sham+vehicle group,I/R group had markedly larger gastric bleeding area(P0.05),activated p38,JNK,and ERK(P0.05),and markedly increased NF-κB p65 and cleaved Caspase-3 expression(P0.05).Pretreatment with CNI-1493 significantly inhibited the above changes in I/R group(P0.05).Conclusion Activation of MAPK/NF-κB pathway play a very important role in I/R-induced gastric injury.Pretreatment with p38 MAPK inhibitor,CNI-1493,can inhibit MAPK/NF-κB pathway,decrease expression of apoptosis protein expression,and reduce gastric mucosal bleeding.