Role of p38 MAPK in ischemia/reperfusion-induced gastric injury in mice / 第二军医大学学报

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-KB) 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 (P < 0.05), activated p38, JNK, and ERK (P <0.05), and markedly increased NF-κB p65 and cleaved Caspase-3 expression (P <0.05). Pretreatment with CNI-1493 significantly inhibited the above changes in 1/R group (P < 0. 05). Conclusion Activation of MAPK/NF-KB 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.