p38抑制剂对缺血再灌注大鼠心肌细胞丝裂原活化蛋白激酶通路的影响

目的探讨p38抑制剂对心肌缺血再灌注大鼠心肌细胞丝裂原活化蛋白激酶(MAPK)通路的影响。方法将44只大鼠随机分为4组:对照组(9只)、缺血组(15只)、缺血再灌注组(10只)和干预组(10只)。对照组大鼠只暴露心脏,缺血组大鼠制备心肌缺血模型,缺血再灌注组大鼠制备心肌缺血再灌注模型,干预组大鼠在左冠状动脉前降支结扎前30 min注射p38抑制剂SB20358(100μg·kg-1),其余操作均与缺血再灌注组一致。观察各组大鼠心肌组织形态学变化及心肌组织中p38、c-Jun氨基端激酶(JNK)和细胞外调节蛋白激酶(ERK1/2)水平的变化。结果对照组大鼠心肌组织中未检测到p38、ERK1/2和JNK蛋白。缺血组缺血60、90 min时大鼠心肌组织中p38蛋白水平显著高于缺血30 min时,差异均有统计学意义(P<0.05);各个时间点,干预组大鼠心肌组织中p38蛋白水平显著低于缺血组和缺血再灌注组,差异均有统计学意义(P<0.05)。随着再灌注时间的延长,缺血再灌注组和干预组大鼠心肌组织中p38蛋白水平逐渐降低,但差异均无统计学意义(P>0.05)。随着缺血和再灌注时间延长,缺血组大鼠心肌组织中ERK1/2和JNK水平略有升高,缺血再灌注组和干预组大鼠心肌组织中ERK1/2和JNK水平略有降低,但差异均无统计学意义(P>0.05)。结论 MAPK中p38参与心肌缺血再灌注损伤,但JNK和ERK1/2的作用不显著。

Effect of p38 inhibitor on the mitogen-activated protein kinase pathway of myocardial cell in rats with myocardial ischemia-reperfusion

Objective To investigate the effect of p38 inhibitor on the mitogen-activated protein kinase（MAPK） pathway of myocardial cell in rats with myocardial ischemia-reperfusion.Methods A total of 44 rats were divided into 4 groups：control group（n = 9）,ischemia group（n = 15）,ischemia-reperfusion group（n = 10） and intervention group（n = 10）.The rats in control group only exposed the heart.The myocardial ischemia models were established in rats of ischemia group.The myocardial ischemia-reperfusion models were established in rats of ischemia group.The rats in intervention group were injected with p38 inhibitor SB20358（100 μg·kg-1） 30 minutes before ligating ramus descendens anterior arteriae coronariae sinistrae,the other handing methods were uniform with those in ischemia-reperfusion group.The morphological changes of myocardial tissue and the levels of p38,c-Jun-NH2-terminal kinase（JNK）,extracellular regulated protein kinase（ERK1 /2） in myocardial tissue of rats were observed in each group.Results The p38,ERK1 /2 and JNK protein did not detected in myocardial tissue of rats in control group.In ischemia group,p38 protein level in myocardial tissue of rats at the points of 60 and 90 minutes after ischemia was significantly higher than that of 30 minutes after ischemia respectively（P〈 0.05）.The level of p38 protein in myocardial tissue of rats in intervention group was significantly lower than that in ischemia group and ischemia-reperfusion group at each time point（P〉 0.05）.With the prolongation of reperfusion,the level of p38 protein in myocardial tissue of rats decreased gradually in ischemia-reperfusion group and intervention group,but the differences were not statistically significant（P〈 0.05）.With the prolongation of ischemia and reperfusion,the level of ERK1 /2 and JNK protein in myocardial tissue of rats increased slightly in ischemia group,the level of ERK1 /2 and JNK protein in myocardial tissue of rats decreased slightly in ischemia-reperfusion group and interv