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
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
作者信息
- 1. 兰州大学,第一临床医学院,甘肃,兰州,730000
- 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
- 折叠
摘要
目的:探讨细胞外信号调节激酶1/2(extracellularsignal-regulated kinase 1/2,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-repeffusion,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(L/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(AT ↑,即∑ST↑除以标测点数)、ST ↑≥2.0 mm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.
Abstract
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 myoeyte 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Key words
ERK1/2/carbamylated erythropoietin/ischemia-reperfusion/apoptosis引用本文复制引用
基金项目
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)
出版年
2009
NETL
NSTL
维普
万方数据