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目的探讨p38丝裂原活化蛋白激酶(p38MAPK)在小鼠胃缺血-再灌注损伤中的作用。方法C57BL/6小鼠随机分为3组:假手术组、模型组和CNI-1493预处理组,CNI-1493预处理组于术前1h腹腔注射p38MAPK抑制剂CNI-1493(2mg/ml)溶液10ml/kg。通过夹闭小鼠腹腔动脉30min后松开动脉夹再灌注1h制作胃缺血-再灌注损伤模型。再灌注1h后取胃标本,甲醛固定后铺平拍照,计算胃黏膜出血面积百分比。应用蛋白质印迹法检测并比较各组磷酸化及总p38、JNK、ERK,磷酸化NF-κBp65以及分裂型Caspase-3的表达水平。结果与假手术组比较,模型组胃黏膜出血面积明显增大(P<0.05),p38、JNK以及ERK明显激活(P<0.05),磷酸化NF-κBp65以及促凋亡蛋白激活型Caspase-3表达明显增多(P<0.05)。CNI-1493预处理能明显逆转上述改变(P<0.05)。结论MAPK/NF-κB通路活化在胃缺血-再灌注损伤中起到重要作用,p38MAPK抑制剂CNI-1493能抑制MAPK/NF-κB通路活化、减少凋亡蛋白表达,减轻胃缺血-再灌注引起的黏膜出血。
Objective To investigate the role of p38 mitogen-activated protein kinase (p38 MAPK) in gastric ischemia-reperfusion injury in mice. Methods C57BL / 6 mice were randomly divided into 3 groups: sham operation group, model group and CNI-1493 preconditioning group. CNI-1493 preconditioning group was intraperitoneally injected with p38MAPK inhibitor CNI-1493 (2mg / 10ml / kg. The model of gastric ischemia-reperfusion injury was established by clamping the celiac artery for 30 minutes and then releasing the artery clip and reperfusion for 1 hour. After reperfusion for 1h, the gastric specimens were taken, and the formaldehyde was fixed and photographed. The percentage of gastric mucosal bleeding area was calculated. The expression of phosphorylated and total p38, JNK, ERK, phosphorylated NF-κBp65 and cleaved Caspase-3 were detected and compared by Western blotting. Results Compared with the sham-operated group, the area of gastric mucosal hemorrhage increased significantly (P <0.05), the expression of p38, JNK and ERK significantly increased (P <0.05), the phosphorylated NF-κBp65 and the pro-apoptotic protein Caspase-3 The expression was significantly increased (P <0.05). CNI-1493 pretreatment can significantly reverse the above changes (P <0.05). Conclusion Activation of MAPK / NF-κB pathway plays an important role in gastric ischemia-reperfusion injury. The p38 MAPK inhibitor CNI-1493 can inhibit the activation of MAPK / NF-κB pathway, decrease the expression of apoptotic protein and alleviate gastric ischemia Mucosal bleeding caused by perfusion.