p38丝裂原活化蛋白激酶介导大鼠心肌缺血再灌注损伤信号传导的研究

摘要

目的:探讨p38丝裂原活化蛋白激酶(p38MAPK)在大鼠心肌缺血再灌注损伤中的作用.方法:健康成年雄性SD大鼠随机分为对照组、单纯缺血组、缺血再灌注组、抑制剂组,每组6只.抑制剂组于术前30 min腹腔注射p38MAPK抑制剂SB 203580(5 mg/kg体重).采用夹闭冠状动脉30 min后再灌注2 h的方法建立大鼠心肌缺血再灌注损伤动物模型.采用逆转录多聚合酶链反应(RT-PCR)检测p38MAPK信使核糖核酸(mRNA)表达,免疫组化法检测p-p38MAPK蛋白表达水平及心肌细胞凋亡率.结果:单纯缺血组与对照组比较,大鼠心肌组织中p-p38MAPK的蛋白含量增加,差异有统计学意义(P<0.01),p38MAPK mRNA的表达及细胞凋亡率也增加,但差异无统计学意义(P>0.05).缺血再灌注组与对照组比较,心肌组织中p38MAPK mRNA及p-p38MAPK蛋白水平和心肌细胞凋亡均显著增加,差异均有统计学意义(P<0.05～0.01).与缺血再灌注组比较,抑制剂组大鼠心肌组织p38MAPK mRNA及p-p38MAPK蛋白水平及心肌细胞凋亡均降低,(P<0.05~0.001),差异均有统计学意义.结论:p38MAPK的激活主要发生于再灌注过程;p38MAPK的活化可使缺血再灌注心肌细胞凋亡增加;抑制p38MAPK的活化可以减少缺血再灌注心肌细胞凋亡,减轻缺血再灌注所致的大鼠心肌损伤.%Objective:To study p38 mitogen-activated protein kinase( MAPK ) signal transduction on myocardial ischemia and reperfu-sion injury ( MI/R ) in rats.rnMethods:Healthy SD male rats were divided into 4 group,Control group,the rats with sham operation,Ischemia group,MI/R group and MI/R plus p38MAPK inhibitor SB203580 ( SB203580 ) group,in which SB203580 was administered intraperitoneally 30 minutes before clamping coronary artery. N = 6 in each group. p38MAPK mRNA expression was examined by RT-PCR, protein expression and myocardial cell apoptosis rate were measured by immune histochemical method.rnResults:Compared with Control group,in Ischemia group,p38MAPK protein expression in myocardial tissue was increased, P<0. 01 ,while; p38MAPK mRNA and ceil apoptosis rate; were not much changed,P>0. 05; in MI/R group,p38MAPK mRNA expression ,protein expression and cell apoptosis rate were all increased, P<0. 05 - P<0. 01. Compared with MI/R group, in SB203580 group,p38MAPK mRNA expression,protein expression and ceil apoptosis rate; were all decreased,P<0. 05 -0. 01.rnConclusion:p38MAPK activation could mainly take place in ischemia and reperfusion process,it may decrease the myocardial injury and cell apoptosis rate in rats.