Ischemic preconditioning enhances scavenging activity of reactive oxygen species and diminishes transmural difference of infarct size
Ischemic preconditioning enhances scavenging activity of reactive oxygen species and diminishes transmural difference of infarct size
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DOI：
10.1152/ajpheart.00817.2004
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发表时间：
2006-02-01
影响因子：
4.8
通讯作者：
Kikuchi, K
中科院分区：
文献类型：
--
作者：
Morihira, M;Hasebe, N;Kikuchi, K
活性氧自由基(ROS)增强心肌缺血再灌注损伤。缺血预适应(PC)对I/R有明显的心肌保护作用，但PC是否减轻了I/R中的ROS应激，以及PC是否通过跨室壁均相性保护心肌免受ROS应激的影响，目前尚不清楚。用Krebs-Henseleit缓冲液灌流兔离体心，缺血30min，再灌流60min。分析四组的血流动力学变化和心肌损伤程度。对照组仅行I/R。H_2O_2组在再灌流后1min行I/R+H_2O_2输注(50mU/M)，以增强氧化应激。PC组和H_2O_2+PC组分别在对照组和H_2O_2方案前进行5分钟的PC。提取的心肌DNA用高效液相-电化学检测法分析DNA氧化损伤的指标8-羟基脱氧鸟苷(8-OHdG)。用分光光度法检测谷胱甘肽过氧化物酶(GPX)活性和还原型谷胱甘肽(GSH)。心肌梗死面积PC组(19+/-2%)明显小于对照组(37+/-4%；P<；0.05)，尤其是心内膜下。过氧化氢可使心肌梗死面积增加59+/-4%(P<；0.05)，而过氧化氢+PC组显著缩小(31+/-4%；P<；0.01)。GSH水平，但不是GPX活性，在与PC的协议中被很好地保存下来。8-OHdG水平在PC组显著降低，在H_2O_2组显著升高(P<；0.01)。PC能有效地减轻DNA氧化损伤的这些变化。综上所述，PC可增强GSH对ROS的跨壁清除能力，减轻心肌损伤，尤其是心内膜下心肌损伤，缩小心肌梗死面积的跨壁差异。
Reactive oxygen species ( ROS) enhance myocardial ischemia-reperfusion ( I/R) injury. Ischemic preconditioning ( PC) provides potent cardioprotective effects in I/R. However, it has not been elucidated whether PC diminishes ROS stress in I/R and whether PC protects the myocardium from ROS stress transmurally and homogeneously. Isolated rabbit hearts perfused with Krebs-Henseleit buffer underwent 30 min of ischemia and 60 min of reperfusion. Hemodynamic changes and myocardial damage extent were analyzed in four groups. The control group underwent I/R alone. The H2O2 group underwent I/R with H2O2 infusion ( 50 mu M) in the first minute of reperfusion to enhance oxidative stress. The PC and H2O2 + PC groups underwent 5 min of PC before control and H2O2 protocols, respectively. Extracted myocardial DNA was analyzed for 8-hydroxydeoxyguanosine ( 8-OHdG), an indicator of oxidative DNA damage, with the use of the HPLC-electrochemical detection method. Glutathione peroxidase ( GPX) activity and the reduced form of GSH were measured by spectrophotometric assays. The myocardial infarct size was significantly reduced in the PC group ( 19 +/- 2%) compared with the control group ( 37 +/- 4%; P < 0.05), particularly in the subendocardium. H2O2 transmurally increased the infarct size by 59 +/- 4% ( P < 0.05), which was significantly diminished in the H2O2 + PC group ( 31 +/- 4%; P < 0.01). The GSH levels, but not GPX activity, were well preserved transmurally in protocols with PC. The 8-OHdG levels were significantly decreased in PC and were significantly enhanced in H2O2 ( P < 0.01). These changes in oxidative DNA damage were effectively diminished by PC. In conclusion, PC enhanced the scavenging activity of GSH against ROS transmurally, reduced myocardial damage, particularly in the subendocardium, and diminished the transmural difference in myocardial infarct size.