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  

Role of p38 MAPK signaling in lung injury following intestinal ischemia/reperfusion in mice

作　　者：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] 

机构地区：[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

出　　处：《第二军医大学学报》2010年第3期254-257,共4页Academic Journal of Second Military Medical University

基　　金：国家自然科学基金重点项目(30730091);上海市重点课题(08411952800)~~

摘　　要：目的探讨p38丝裂原活化蛋白激酶(p38MAPK)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1h腹腔注入p38MAPK抑制剂SB239063(3mg/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45min后再灌注6h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p38MAPK蛋白水平,RT-PCR检测肺组织TNF-α和IL-1βmRNA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p38MAPK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p38MAPK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-1βmRNA表达(与缺血再灌注组比较P<0.05)。结论p38MAPK在小鼠肠缺血再灌注肺损伤中起重要作用,抑制p38MAPK活化可减轻肠缺血再灌注肺损伤。Objective To investigate the possible role of p38 mitogen-activated protein kinase（MAPK） in lung injury following intestinal ischemia reperfusion（II/R） in mice.Methods Intestinal 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.Results Compared with the sham-operated group,pulmonary p38 MAPK activation was significantly increased 6 h after II/R（P0.01）,whereas SB239063 could markedly attenuate p38 MAPK activation in lung tissue（P0.05）.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（P0.05）.SB239063 treatment ameliorated the pathologic lung injury induced by II/R.Conclusion p38 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.

关 键 词：小肠 再灌注损伤 p丝裂原活化蛋白激酶 肺损伤 SB 肠缺血再灌注 肺组织 小鼠 基因表达水平 抑制剂 

分 类 号：R656.7[医药卫生—外科学]