细胞外信号调节蛋白激酶在一氧化氮对心肌缺血再灌注后保护及抗凋亡的作用  

Role of extracellular signal-regulated kinase in cardioprotective and anti-apoptotic effects of nitric oxide after myocardial ischemia and reperfusion

作　　者：魏以桢[1] 李巅远[1] 赵红[2] 李汉美[1] 

机构地区：[1]中国医学科学院北京协和医学院阜外心血管病医院心血管外科,北京100037 [2]中国医学科学院北京协和医学院阜外心血管病医院病理科,北京100037

出　　处：《中华实验外科杂志》2010年第7期946-948,共3页Chinese Journal of Experimental Surgery

基　　金：基金项目：中央级公益性科研院所基本科研基金资助项目

摘　　要：目的 探讨细胞外信号调节蛋白激酶（ERK）是否在整体器官和活体水平参与一氧化氮（NO）对心肌缺血再灌注损伤后的心脏保护和抗细胞凋亡过程及其与NO的相互作用机制.方法 小鼠离体心脏灌注模型全心脏缺血20min,再灌注120min.再灌注期间分别用空白对照剂或NO供体（SNAP,10μmoL/L）治疗.用选择性MEK1/2（MEK1/2是激活ERK1/2的上游激酶）阻断剂U0126（1μmol/J L）预治疗（于缺血前10min）.结果 用SNAP治疗组表现出明显的心肌保护作用,表现为心肌细胞凋亡减少（TUNEL和Caspase-3活性,P〈0.01）和心功能提高（P〈0.01）.此外,SNAP组和对照剂组比较,2.5倍的激活ERK. U0126完全阻断了SNAP诱导的ERK激活,明显但不是完全阻断SNAP的心脏保护作用.结论 NO在缺血再灌注心脏中的抗凋亡和心脏保护机制,部分是通过激活ERK进行.Objective To determine whether extracellular signal-regulated kinase （ERK） participates in the whole organ or whole animal level in the cardioprotective and anti-apoptotic effects of nitric oxide （NO） during myocardial ischemia/reperfusion （MI/R） injury and the mechanism of ERK and NO in anti-apoptotic effect. Methods Isolated perfused mouse hearts were subjected to 20 min of global ischemi-a and 120 min of reperfusion. During reperfusion period, the hearts were treated with either vehicle or NO donor （SNAP, 10μmol/L）. To determine the role of ERK in the anti-apoptotic and cardioprotective effects of NO, some mouse hearts were pre-treated （10 min before ischemia） with U0126, a selective MEK1/2 inhibitor （1μmol/L）. Results The group treated with SNAP showed marked myocardial protection effect. Their apoptosis is obviously inhibited （TUNEL and Caspase-3 activity,P 〈0.01）. Their cardiac functional recovery was better （P〈0.01）. Besides, as compared with vehicle group, treatment with SNAP resulted in a 2. 5-fold increase in ERK activation. Pre-treatment with U0126 slightly increased post-ischemic myocardial apoptosis but showed httle effect on cardiac functional recovery. However, U0126 completely blocked ERK activation induced by SNAP and markedly, although not completely, blocked the cardiac protective effect of SNAP. Conclusion The anti-apoptotic and myocardial protection effect of NO is at least in part, mediated through activation of ERK in ischemic/reperfused heart.

关 键 词：一氧化氮 ERK 心肌缺血 再灌注损伤 脱噬作用 

分 类 号：R285.5[医药卫生—中药学]