Breathing nitric oxide plus hydrogen gas reduces ischemia-reperfusion injury and nitrotyrosine production in murine heart.
Breathing nitric oxide plus hydrogen gas reduces ischemia-reperfusion injury and nitrotyrosine production in murine heart.
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DOI：
10.1152/ajpheart.00844.2012
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发表时间：
2013-08
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通讯作者：
Toshihiro Shinbo;K. Kokubo;Yuri Sato;Shintaro Hagiri;R. Hataishi;M. Hirose;Hirosuke Kobayashi
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文献类型：
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作者：
Toshihiro Shinbo;K. Kokubo;Yuri Sato;Shintaro Hagiri;R. Hataishi;M. Hirose;Hirosuke Kobayashi
吸入一氧化氮（NO）可减少心肌缺血再灌注（I/R）损伤的梗死面积。然而，NO产生的活性氮（RNS）可引起心肌功能障碍和损伤。因为据报道H2 O2可以消除过氧亚硝酸盐，所以预期其可以减少NO的副作用。在小鼠中，左前降支冠状动脉结扎60分钟，然后再灌注，在再灌注前5分钟开始吸入NO [百万分之80（ppm）]、H2 O2（2%）或NO + H2 O2，持续35分钟。和危险区（AAR）进行评估。通过8-羟基-2 '-脱氧鸟苷和4-羟基-2-壬烯醛染色评价与活性氧（ROS）相关的氧化应激，通过硝基酪氨酸染色评价与RNS相关的氧化应激，通过粒细胞受体-1染色评价中性粒细胞浸润。单独吸入NO或H2可使梗塞面积/AAR减小。吸入NO + H2 O2可减少梗死面积/AAR，两者之间存在明显的交互作用，减少ROS和中性粒细胞浸润，改善心功能至正常水平。虽然硝基酪氨酸染色突出后，单独吸入NO，它被消除后，呼吸的混合物H2O与NO。预处理与NO显著降低梗死面积/AAR，但不预处理与H2O。总之，在I/R期间吸入NO + H2O可减少梗死面积和维持心功能，并减少与吸入NO相关的心肌硝基酪氨酸的产生。吸入NO + H2气体可能有助于计划的冠状动脉介入治疗或I/R损伤的治疗。
Inhaled nitric oxide (NO) has been reported to decrease the infarct size in cardiac ischemia-reperfusion (I/R) injury. However, reactive nitrogen species (RNS) produced by NO cause myocardial dysfunction and injury. Because H₂ is reported to eliminate peroxynitrite, it was expected to reduce the adverse effects of NO. In mice, left anterior descending coronary artery ligation for 60 min followed by reperfusion was performed with inhaled NO [80 parts per million (ppm)], H₂ (2%), or NO + H₂, starting 5 min before reperfusion for 35 min. After 24 h, left ventricular function, infarct size, and area at risk (AAR) were assessed. Oxidative stress associated with reactive oxygen species (ROS) was evaluated by staining for 8-hydroxy-2'-deoxyguanosine and 4-hydroxy-2-nonenal, that associated with RNS by staining for nitrotyrosine, and neutrophil infiltration by staining for granulocyte receptor-1. The infarct size/AAR decreased with breathing NO or H₂ alone. NO inhalation plus H₂ reduced the infarct size/AAR, with significant interaction between the two, reducing ROS and neutrophil infiltration, and improved the cardiac function to normal levels. Although nitrotyrosine staining was prominent after NO inhalation alone, it was eliminated after breathing a mixture of H₂ with NO. Preconditioning with NO significantly reduced the infarct size/AAR, but not preconditioning with H₂. In conclusion, breathing NO + H₂ during I/R reduced the infarct size and maintained cardiac function, and reduced the generation of myocardial nitrotyrosine associated with NO inhalation. Administration of NO + H₂ gases for inhalation may be useful for planned coronary interventions or for the treatment of I/R injury.