ERK1/2信号通路在CEPO抗心肌缺血-再灌注损伤中的作用  

Effect of ERK1/2 signaling pathway on carbamylated erythropoietin-induced cardio-protection against ischemia-reperfusion injury

作　　者：许哲通[1] 王志禄[2] 杨小芳[3] 熊建文[1] 王锋[1] 谈丽丽[1] 崔丽君[1] 张丽[1] 

机构地区：[1]兰州大学第一临床医学院 [2]兰州大学第一医院心内科,甘肃兰州730000 [3]兰州大学第一医院心外科,甘肃兰州730000

出　　处：《第四军医大学学报》2009年第19期1967-1970,共4页Journal of the Fourth Military Medical University

基　　金：兰州大学医学科研基金(820726);甘肃省新药临床前研究重点实验室开放基金(GSKFKT-0707)

摘　　要：目的:探讨细胞外信号调节激酶1/2(extracellularsignal-regulated kinase1/2,ERK1/2)信号通路在氨甲酰化促红细胞生成素(carbamylated erythropoietin,CEPO)抗心肌缺血-再灌注(ischemia-reperfusion,I/R)损伤中的作用.方法:建立家兔心肌缺血-再灌注模型,并随机分为假手术组、缺血-再灌注组(I/R组),CEPO预处理组(I/R+CEPO组),PD98059预处理组(I/R+PD98059组),CEPO+PD98059预处理组(I/R+CEPO+PD98059组),每组8只.心电图记录并比较ST段平均抬高的毫米数(ST↑,即∑ST↑除以标测点数)、ST↑≥2.0mm的标测点占总标测点的百分比(NST↑%)和出现病理性Q波的标测点占总标测点的百分比(NQ%),TUNEL法检测心肌细胞凋亡率.结果:I/R+PD98059组ST↑,NST↑%,NQ%及心肌细胞凋亡率较I/R组均无明显差异(P>0.05);I/R+PD98059+CEPO组ST↑,NST↑%,NQ%及心肌细胞凋亡率较I/R+CEPO组均升高(P<0.05);I/R+CEPO组和IR+PD98059+CEPO组ST↑,NST↑%,NQ%及心肌细胞凋亡率较I/R组均降低(P<0.05).结论:CEPO可通过激活ERK1/2信号通路发挥急性抗心肌缺血-再灌注损伤的作用;在无CEPO干预时,单纯的缺血-再灌注并不明显激活ERK1/2信号通路.AIM：To investigate the effect of extracellular signal-regulated kinase 1/2（ERK1/2）signaling pathway on carbamylated erythropoietin-induced cardioprotection against ischemia-reperfusion（I/R）injury.METHODS：Forty rabbits were randomly allocated to control group,I/R group,I/R＋CEPO group,I/R＋ PD98059 group,I/R＋CEPO＋PD98059 group.We compared the difference of infarct size using observations of ST↑,NST↑%,NQ% in the 12-lead ECG.The paraffin slices were subjected to terminal deoxy-nucleotidyl transferase-mediated dUTP nick-end labeling（TUNEL）staining for detection of cardiac myocyte apoptotic rate.RESULTS：There was no diference between I/R＋PD98059 group and I/R group on ST↑,NST↑%,NQ% and cardiac myocyte apoptotic rate（P〉0.05）;I/R＋CEPO＋PD98059 group was higher than I/R＋CEPO group on ST↑,NST↑%,NQ% and cardiac myocyte apoptotic rate（P〈0.05）;I/R＋CEPO group and IR＋PD98059＋CEPO group were lower than I/R group on ST↑,NST↑%,NQ% and cardiac myocyte apoptotic rate（P〈0.05）.CONCLUSION：Acute cardioprotective effect of CEPO was mediated by activation of ERK1/2 signaling pathway.ERK1/2 signaling pathway wasn＇t significantly actived in the absence of CEPO.

关 键 词：ERK1/2 氨甲酰化促红细胞生成素 缺血-再灌注 凋亡 

分 类 号：R54[医药卫生—心血管疾病]