Sivarajah Ahila, Collino Massimo, Yasin Mohammed, Benetti Elisa, Gallicchio Margherita, Mazzon Emanuela, Cuzzocrea Salvatore, Fantozzi Roberto, Thiemermann Christoph
Centre for Translational Medicine, The William Harvey Research Institute, St. Bartholomew's and The Royal London School of Medicine and Dentistry, Charterhouse Square, London, UK.
Shock. 2009 Mar;31(3):267-74. doi: 10.1097/SHK.0b013e318180ff89.
Hydrogen sulfide (H2S) is a novel gaseous mediator produced by cystathionine-beta-synthase and cystathionine-gamma-lyase in the cardiovascular system, including the heart. Using a rat model of regional myocardial ischemia/reperfusion, we investigated the effects of an H2S donor (sodium hydrogen sulfide [NaHS]) on the infarct size and apoptosis caused by ischemia (25 min) and reperfusion (2 h). Furthermore, we investigated the potential mechanism(s) of the cardioprotective effect(s) afforded by NaHS. Specifically, we demonstrate that NaHS (1) attenuates the increase in caspase 9 activity observed in cardiac myocytes isolated from the area at risk (AAR) of hearts subjected in vivo to regional myocardial I/R and (2) ameliorates the decrease in expression of Bcl-2 within the AAR obtained from rat hearts subjected to regional myocardial I/R. The cardioprotective effects of NaHS were abolished by 5-hydroxydeconoate, a putative mitochondrial adenosine triphosphate-sensitive potassium channel blocker. Furthermore, NaHS attenuated the increase in the I/R-induced (1) phosphorylation of p38 mitogen-activated protein kinase and Jun N-terminal kinase, (2) translocation from the cytosol to the nucleus of the p65 subunit of nuclear factor-kappaB, (3) intercellular adhesion molecule 1 expression, (4) polymorphonuclear leukocyte accumulation, (5) myeloperoxidase activity, (6) malondialdehyde levels, and (7) nitrotyrosine staining determined in the AAR obtained from rat hearts subjected to regional myocardial I/R. In conclusion, we demonstrate that the cardioprotective effect of NaHS is secondary to a combination of antiapoptotic and anti-inflammatory effects. The antiapoptotic effect of NaHS may be in part due to the opening of the putative mitochondrial adenosine triphosphate-sensitive potassium channels.
硫化氢（H₂S）是一种由胱硫醚-β-合酶和胱硫醚-γ-裂解酶在包括心脏在内的心血管系统中产生的新型气态介质。我们使用局部心肌缺血/再灌注大鼠模型，研究了硫化氢供体（硫氢化钠[NaHS]）对缺血（25分钟）和再灌注（2小时）引起的梗死面积和细胞凋亡的影响。此外，我们还研究了NaHS发挥心脏保护作用的潜在机制。具体而言，我们证明NaHS（1）减弱了在体内经历局部心肌缺血/再灌注的心脏的危险区域（AAR）分离的心肌细胞中观察到的半胱天冬酶9活性的增加，以及（2）改善了在经历局部心肌缺血/再灌注的大鼠心脏的AAR中Bcl-2表达的降低。5-羟基癸酸（一种假定的线粒体三磷酸腺苷敏感性钾通道阻滞剂）消除了NaHS的心脏保护作用。此外，NaHS减弱了缺血/再灌注诱导的（1）p38丝裂原活化蛋白激酶和Jun N末端激酶的磷酸化增加，（2）核因子-κB的p65亚基从细胞质向细胞核的转位，（3）细胞间黏附分子1表达，（4）多形核白细胞聚集，（5）髓过氧化物酶活性，（6）丙二醛水平，以及（7）在经历局部心肌缺血/再灌注的大鼠心脏的AAR中测定的硝基酪氨酸染色。总之，我们证明NaHS的心脏保护作用继发于抗凋亡和抗炎作用的联合。NaHS的抗凋亡作用可能部分归因于假定的线粒体三磷酸腺苷敏感性钾通道的开放。
