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| p38丝裂原活化蛋白激酶在小鼠肠缺血再灌注肺损伤中的作用 |
| 郑德义1,2,王建明1,2,贾一韬1,付晋凤2,吕开阳1,廖庚进1,2,郑兴锋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）在小鼠肠缺血再灌注肺损伤的作用。方法10周龄健康雄性C57BL/6小鼠随机分为假手术组、缺血再灌注组和缺血再灌注+SB239063处理组（SB239063组）,SB239063组于术前1 h腹腔注入p38 MAPK 抑制剂SB239063（3 mg/kg）,另两组注入等量生理盐水。采用夹闭C57BL/6小鼠肠系膜前动脉45 min后再灌注6 h的方法造成肠缺血再灌注损伤模型。处死小鼠取肺标本,蛋白质印迹法检测肺组织磷酸化p38 MAPK蛋白水平,RT-PCR检测肺组织TNF-α和IL-1β mRNA表达,H-E染色观察肺组织病理学改变。结果肠缺血再灌注导致明显肺损伤,肺组织p38 MAPK活化明显增加,TNF-α和IL-1β基因表达水平明显升高（与假手术组比较P<0.01）；SB239063可抑制肺组织p38 MAPK活化,减轻小肠缺血再灌注引起的肺损伤,并下调肺组织TNF-α和IL-1β mRNA表达（与缺血再灌注组比较P<0.05）。结论p38 MAPK在小鼠肠缺血再灌注肺损伤中起重要作用,抑制p38 MAPK活化可减轻肠缺血再灌注肺损伤。 |
| 关键词: 小肠 再灌注损伤 p38丝裂原活化蛋白激酶 肺损伤 SB239063 |
| DOI：10.3724/SP.J.1008.2010.0254 |
| 投稿时间：2009-12-11修订日期：2010-01-11 |
| 基金项目:国家自然科学基金重点项目(30730091),上海市重点课题（08411952800）. |
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| Role of p38 MAPK signaling in lung injury following intestinal ischemia/reperfusion in mice |
| ZHENG De-yi1,2, WANG Jian-ming1,2, JIA Yi-tao1, FU Jin-feng 2, L Kai-yang1, LIAO Geng-jin1,2, ZHENG Xing-feng1, 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 possible role of p38 mitogen-activated protein kinase (MAPK) in lung injury following intestinal ischemia reperfusion (II/R) in mice. MethodsIntestinal ischemia/reperfusion was induced by occluding the superior mesenteric artery for 45 min followed by 6 h reperfusion. C57BL/6 mice were randomly divided into sham-operated group (sham group),II/R group and II/R plus SB239063 treatment (SB239063 group),n=6/group. SB239063 (3 mg/kg), a novel second-generation p38 MAPK inhibitor,was administered intraperitoneally one hour before clamping. Pulmonary p38 MAPK and phospho-p38 MAPK protein were measured by Western blotting analysis. Gene expression of TNF-α and IL-1β in the lung was analyzed by RT-PCR. The lung pathology was observed by optical microscope. ResultsCompared with the sham-operated group, pulmonary p38 MAPK activation was significantly increased 6 h after II/R (P<0.01), whereas SB239063 could markedly attenuate p38 MAPK activation in lung tissue (P<0.05). In addition, the increased TNF-α and IL-1β mRNA levels induced by II/R in lungs were significantly blocked by inhibiting p38 MAPK activation (P<0.05). SB239063 treatment ameliorated the pathologic lung injury induced by II/R. Conclusionp38 MAPK plays an important role in lung injury induced by intestinal ischemia reperfusion (II/R) in mice, and inhibition of p38 MAPK activation prevents lung injury following II/R in mice. |
| Key words: intestinal reperfusion injury p38 mitogen-activated protein kinase lung injury SB239063 |
