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p38丝裂原活化蛋白激酶在小鼠胃缺血-再灌注损伤中的作用 |
王建明1,2,郑德义1,2,贾一韬1,付晋凤2,郑兴锋1,吕开阳1,夏照帆1* |
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(1.第二军医大学长海医院烧伤科,上海 200433;2.昆明医学院第二附属医院烧伤科,昆明 650101) |
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摘要: |
目的探讨p38丝裂原活化蛋白激酶(p38 MAPK)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CNI1493预处理组,CNI1493预处理组于术前1 h腹腔注射p38 MAPK 抑制剂CNI1493(2 mg/ml)溶液10 ml/kg。通过夹闭小鼠腹腔动脉30 min后松开动脉夹再灌注1 h制作胃缺血再灌注损伤模型。再灌注1 h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NFκB p65以及分裂型Caspase3 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NFκB p65以及促凋亡蛋白激活型Caspase3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/NFκB通路活化在胃缺血再灌注损伤中起到重要作用,p38 MAPK抑制剂CNI1493能抑制MAPK/NFκB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。 |
关键词: 胃 再灌注 丝裂原活化蛋白激酶 NF-κB 细胞凋亡 |
DOI:10.3724/SP.J.1008.2010.0250 |
投稿时间:2009-12-13修订日期:2010-01-14 |
基金项目:国家自然科学基金重点项目(30730091). |
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Role of p38 MAPK in ischemia/reperfusion induced gastric injury in mice |
WANG Jian-ming1,2, ZHENG De-yi1,2, JIA Yi-tao1, FU Jin-feng2, ZHENG Xing-feng1, L Kai-yang1, XIA Zhao-fan1* |
(1.Department of Burns, Changhai Hospital, Second Military Medical University, Shanghai 200433, China;2.Department of Burns, The Second Affiliated Hospital of Kunming Medical College, Kunming 650101, Yunnan, China) |
Abstract: |
ObjectiveTo investigate the role of p38 MAPK on gastric ischemia/reperfusion (I/R)induced injury in mice.MethodsC57BL/6 mice were randomly divided into three groups: sham+vehicle group, I/R+vehicle group (as control), and I/R+CNI1493 group. The gastric IR injury mice were prepared by occluding the celiac artery for 30 min followed by reperfusion for 1 h. Shamoperated animals underwent the same surgical procedure without clamping. Physiological saline (0.9% NaCl, 10 ml/kg) or CNI1493(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 totalmitogenactivated protein kinases (MAPKs including p38, JNK, and ERK), phosphonuclear factorκB (NFκB) and cleaved Caspase3 in the injured stomach tissue were determined by Western blotting analysis.ResultsCompared 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 NFκB p65 and cleaved Caspase3 expression (P<0.05). Pretreatment with CNI1493 significantly inhibited the above changes in I/R group (P<0.05). ConclusionActivation of MAPK/NFκB pathway play a very important role in I/Rinduced gastric injury. Pretreatment with p38 MAPK inhibitor, CNI1493, can inhibit MAPK/NFκB pathway, decrease expression of apoptosis protein expression, and reduce gastric mucosal bleeding. |
Key words: stomach reperfusion injury mitogen activated protein kinase NF κB apoptosis |