CAJ | 학술논문

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.
목적 탐토세포외신호조절단백격매(ERK)시부재정체기관화활체수평삼여일양화담(NO)대심기결혈재관주손상후적심장보호화항세포조망과정급기여NO적상호작용궤제.방법 소서리체심장관주모형전심장결혈20min,재관주120min.재관주기간분별용공백대조제혹NO공체(SNAP,10μmoL/L)치료.용선택성MEK1/2(MEK1/2시격활ERK1/2적상유격매)조단제U0126(1μmol/J L)예치료(우결혈전10min).결과 용SNAP치료조표현출명현적심기보호작용,표현위심기세포조망감소(TUNEL화Caspase-3활성,P<0.01)화심공능제고(P<0.01).차외,SNAP조화대조제조비교,2.5배적격활ERK. U0126완전조단료SNAP유도적ERK격활,명현단불시완전조단SNAP적심장보호작용.결론 NO재결혈재관주심장중적항조망화심장보호궤제,부분시통과격활ERK진행.
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.