首都医科大学学报 ›› 2007, Vol. 28 ›› Issue (1): 64-67.

• 基础研究 • 上一篇    下一篇

11,12-环二十碳三烯酸对心脏缺血/再灌注损伤大鼠血红素氧合酶-1的影响

江瑛, 闫丽, 王红霞, 芦玲巧, 曾翔俊, 朱盈芬, 张立克   

  1. 首都医科大学病理生理学教研室
  • 收稿日期:2006-09-26 修回日期:1900-01-01 出版日期:2007-02-24 发布日期:2007-02-24
  • 通讯作者: 张立克

Effects of 11,12-EET on Heme Oxygenase-1 in Ischemia/Reperfusion Rat Heart

Jiang Ying, Yan Li, Wang Hongxia, Lu Lingqiao, Zeng Xiangjun, Zhu Yinfen, Zhang Like   

  1. Department of Pathophysiology, Capital Medical University
  • Received:2006-09-26 Revised:1900-01-01 Online:2007-02-24 Published:2007-02-24

摘要: 目的 观察11,12-环二十碳三烯酸(11,12-EET)对缺血/再灌注(I/R)损伤大鼠心肌血红素氧合酶-1(HO-1)的影响,并探讨其作用机制。方法 采用健康雄性Wistar大鼠制备心肌缺血/再灌注模型,实验分为3组:1)缺血/再灌注(I/R)组,2)环氧二十碳三烯酸(EET)组及3)左旋精氨酸甲酯(L-NAME)组。观察缺血60min再灌注30min时心脏收缩期左心室内压上升的最大变化速率及舒张期左心室内压下降的最大变化速率。采用Westernblot法测定心肌HO-1表达水平。采用化学比色法观察大鼠心肌组织NOS及iNOS活性。结果 收缩期左心室内压上升的最大变化速率及舒张期左心室内压下降的最大变化速率EET组高于I/R组(P<0.01);L-NAME组低于EET组(P<0.05)。心肌HO-1表达水平EET组高于I/R组(P<0.05),L-NAME组低于EET组(P<0.05)。EET组cNOS活性高于I/R组(P<0.01),L-NAME组cNOS活性低于EET组(P<0.05);EET组iNOS活性低于I/R组(P<0.01),L-NAME组iNOS活性低于EET组,但差异无统计学意义(P>0.05)。结论 外源性11,12-EET能改善缺血/再灌注大鼠心功能损伤程度,增加心肌HO-1表达水平和cNOS活性,降低iNOS活性。提示11,12-EET拮抗心肌缺血/再灌注损伤的作用可能与HO-1表达增加有关,且此时HO-1的表达增加至少部分依赖于cNOS的激活。

关键词: 12-环二十碳三烯酸, 心肌, 缺血/再灌注损伤, 血红素氧合酶-1, 一氧化氮合酶

Abstract: Objective To observe the effects of 11, 12-epoxyeicosatrienoic acid (11, 12 -EET) on heme oxygenase-1(HO-1) in myocardial ischemic/reperfusion(I/R) injury in rats. Methods Myocardial ischemic/reperfusion model was produced by legating the left anterior descending coronary artery for 60 min followed by 30 min reperfusion. The rats were divided into 3 groups: 1) ischemia/ reperfusion(I/R) group; 2) EET group, 6.24×10-8 mol/ L 11, 12-EET was injected intravenously 20 min before I/R; 3) L-NAME group, L-NAME was injected intravenously 10 min before EET plus I/R .The heart function was evaluated by observing the change of +dp/dtmax and -dp/dtmax. The level of HO-1 was detected by Western blot method. The activities of nitric oxide synthase of myocardium were examined by colorimetric method. Results At 30 min reperfusion, +dp/dtmax and -dp/dtmax increased significantly in EET group compared with I/R group(P<0.01). HO-1 level was higher in EET group than I/R group(P<0.05). HO-1 level was lower in L-NAME group than EET group(P<0.05). The activities of cNOS in EET group were higher than those in I/R(P<0.01). The activities of iNOS in EET group were lower than those in I/R(P<0.01). Conclusion 11, 12-EET protected rat heart against I/R injury. 11,12-EET increased the expression level of HO-1 and the activities of cNOS and decreased the activities of iNOS .As the expression of HO-1 induced by 11,12-EET could be blocked by L-NAME, It was indicated that elevated HO-1 was involved in NO-meadiated signal pathway.

Key words: 12-epoxyeicosatrienoic acid, cardiac muscle, ischemic/reperfusion, heme oxygenase-1, nitric oxide synthase

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