MAPK及PI3K-AKT信号通路活化在小鼠胃缺血再灌注损伤中的作用  

Effects of mitogen-activated protein kinase and phosphatidylinositol 3-kinase-AKT pathway activation during gastric ischemia-reperfusion in mice

作　　者：王建明[1,2] 郑德义[1,2] 贾一韬[1] 付晋凤[2] 吕开阳[1] 郑兴锋[1] 夏照帆[1] 

机构地区：[1]第二军医大学长海医院,上海200433 [2]昆明医学院第二附属医院

出　　处：《山东医药》2010年第10期6-7,共2页Shandong Medical Journal

基　　金：国家自然科学基金资助项目(30730091)

摘　　要：目的探讨丝裂原活化蛋白激酶(MAPK)及PI3K-AKT信号通路在小鼠胃缺血再灌注损伤中的作用。方法实验鼠随机分为假手术组和再灌注0.5、1、2、4、6、12 h组,夹闭小鼠腹腔动脉30 min后松开动脉夹再灌注建立模型。分析计算胃黏膜出血面积百分比,Western blot法检测胃组织中磷酸化p38、JNK、ERK、AKT以及总AKT蛋白。结果再灌注组再灌注后各时间点胃黏膜出血面积明显大于假手术组(P均<0.01)。与假手术组相比,再灌注组再灌注后30 min^2 h,胃组织p38、JNK、ERK明显活化(P<0.01);12 h及24 h再灌注组ERK活化明显高于假手术组(P<0.01);再灌注组再灌注后各时间点AKT的磷酸化均明显高于假手术组(P均<0.01)。结论MAPK信号通路活化可能参与了小鼠胃缺血再灌注损伤过程;促修复的PI3K-AKT通路持续活化,可能参与了缺血再灌注后胃黏膜损伤的修复。Objective To investigate the relationship between gastric mucosal bleeding induced by ischemia-reperfusion and activation of mitogen-activated protein kinase（MAPK） and phosphatidylinositol 3-kinase （PI3K）-AKT pathway. Methods Mice were randomly divided into sham group and reperfusion 30 min, 1 h,2 h,4 h,6 h, 12 h,24 h groups. Each gastric ischemia-reperfusion injury was achieved by occlusion the celiac artery with a small clamp for 30 min, and removing the clamp. Gastric mucosa bleeding area were analyzed with a digital imaging analyzer （recognized as reddish areas by the computer system） and measured and summed as the total injured areas and counted the percentage of bleeding area to total stomach. The p-p38, p-JNK,p-ERK, p-AKT and total-AKT in injured stomach were determined by Western blot analysis. Results Gastric bleeding＇area were increased markedly after reperfusion in reperfusion group than sham group （P 〈 0.01 ）. Significant activation of p38 ,JNK and ERK were observed at early phase （ from 30 min to 2 h） of reperfusion. The activation of ERK in 12 h and 24 h groups were significantly higher than sham group（P〈0.01） ; After reperfusion at different time points ,AKT phosphorylation were significantly higher than the sham group（ P 〈 0.01 ）. Conclusions The activation of MAPK pathway may contribute to gastric mucosa bleeding induced by ischemia-reperfusion, and consistent activation of AKT after reperfusion may be involved in regeneration of gastric mucosa in mice.

关 键 词：胃 缺血再灌注 胃黏膜出血 丝裂原活化蛋白激酶信号通路 PI3K-AKT信号通路 

分 类 号：R641[医药卫生—外科学]