首都医科大学学报 ›› 2011, Vol. 32 ›› Issue (6): 802-805.doi: 10.3969/j.issn.1006-7795.2011.06.019

• 基础研究 • 上一篇    下一篇

11,12-EET心脏保护过程中NOS及ERK的交互作用

王珏1, 闫丽2, 曾翔俊3, 王红霞3, 芦玲巧3, 张立克3   

  1. 1. 首都医科大学基础医学院病理教研室,北京 100069;2. 首都医科大学附属北京佑安医院肝病研究所,北京 100069;3. 首都医科大学基础医学院病理生理学教研室,北京 100069
  • 收稿日期:2011-06-30 修回日期:1900-01-01 出版日期:2011-12-21 发布日期:2011-12-21
  • 通讯作者: 曾翔俊

The interaction of nitric oxide synthase and extracellular signal regulated kinase in cardioprotection of 11,12-epoxyeicosatrienoic acid

WANG Jue1, YAN Li2, ZENG Xiang-jun3, WANG Hong-xia3, LU Ling-qiao3, ZHANG Li-ke3   

  1. 1. Department of Pathology, School of Basic Medical Science, Capital Medical University, Beijing 100069, China;2. Institue for Liver Disease, Beijing Youan hospital, Capital Medical University, Beijing 100069, China;3. Department of Pathophysiology, School of Basic Medical Science, Capital Medical University, Beijing 100069, China
  • Received:2011-06-30 Revised:1900-01-01 Online:2011-12-21 Published:2011-12-21

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206

被引次数

7

摘要： 目的 观察胞外信号调节激酶(extracellular signal regulated kinase 1/2,ERK1/2)抑制剂对11,12-环氧二十碳三烯酸(11,12-epoxyeicosatrienoic acid,11,12-EET)引起的结构型一氧化氮合酶(structural nitric oxide synthase,sNOS)变化的影响,了解NOS与ERK1/2在11,12-EET心脏保护中的作用方式。方法 采用冠状动脉缺血60 min再灌注30 min的方法复制大鼠心肌缺血/再灌注模型。实验分为4组:缺血再灌注组(ischemia/reperfusion, I/R);假手术组(Sham);11,12-EET缺血再灌注组(EET+I/R);11,12-EET缺血再灌注加PD098059组(EET+I/R+PD)。观察缺血60 min再灌注30 min时心脏收缩期左心室内压上升的最大变化速率(+dp/dt max)及舒张期左心室内压下降的最大变化速率(-dp/dt max);采用化学比色法观察大鼠心肌组织sNOS活性。结果 I/R组的±dp/dtmax均低于Sham组及EET+I/R组(P<0.01); EET+I/R+PD组均低于EET+I/R组的±dp/dt max(P<0.01)。I/R组心肌sNOS低于Sham组(P<0.01)及EET+I/R组(P<0.01); EET+I/R组高于EET+I/R+PD组(P<0.01)。结论 11,12-EET对心功能的保护作用可能通过上调ERK进而增加sNOS的表达来实现。

关键词: 12-环二十碳三烯酸, 缺血/再灌注损伤, 一氧化氮合酶, 细胞外调节蛋白激酶

Abstract: Objective To observe the effects of extracellular signal regulated kinase(ERK)1/2 inhibitor on the change of structural nitric oxide synthase(sNOS) caused by the 11,12-epoxyeicosatrienoic acid(1,2-EET) and study the mode of action of NOS and ERK in cardioprotection of 11,12-EET. Methods Myocardial ischemic/reperfusion model was produced by ligating the left anterior descending coronary artery for 60 min followed by 30 min reperfusion. The rats were divided into 4 groups: ischemia/reperfusion group(I/R); Sham group(Sham); EET and ischemia/reperfusion group(EET+I/R); EET, ischemia/reperfusion and PD098059 group(EET+I/R+PD). The heart function was evaluated by observing the maximum changes of intraventricular pressure(+dp/dt max and -dp/dt max). The activities of nitric oxide synthase of myocardium were examined by colorimetric method. Results At 30 min reperfusion, +dp/dt max and -dp/dt max decreased significantly in I/R group compared with Sham group and EET+IR group(P<0.01), and those in EET+I/R+PD group were less than those in EET+I/Rgroup(P<0.01). The activities of sNOS in IR group were lower than those in Sham group and EET+I/R group(P<0.01), and those in EET+I/R group were higher than those in EET+I/R+PD group(P<0.01). Conclusion Cardioprotective effect of 11,12-EET may be mediated by increasing the ERK then increasing the activity of sNOS.

Key words: 12-epoxyeicosatrienoic acid, ischemic/reperfusion injury, nitric oxide synthase, excelluar signal regulated kinase

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