Fantinelli Juliana C, Cingolani Horacio E, Mosca Susana M
Fellowship of Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Centro de Investigaciones Cardiovasculares, 1900 La Plata, Argentina.
Cardiovasc Pathol. 2006 Jul-Aug;15(4):179-84. doi: 10.1016/j.carpath.2006.04.005.
A burst of reactive oxygen species and activation of Na+/H+ exchanger take place at the beginning of reperfusion. The aim of this study was to assess the possible interrelation of the inhibition of Na+/H+ exchanger and reactive oxygen species about the determination of myocardial infarct size.
Isolated rat hearts were submitted to 40 min of coronary occlusion and 2 h of reperfusion. Infarct size was determined through triphenyltetrazolium chloride staining technique and was expressed as a percentage of risk area. Lipid peroxidation, as a marker of oxidative stress, was estimated by the concentration of thiobarbituric reactive substances.
Treatment during the first 20 min of reperfusion with a selective inhibitor of Na+/H+ exchanger 1 isoform, HOE 642 (cariporide; 10 microM), significantly diminished infarct size (15.1+/-2.4% vs. 31+/-2% in untreated hearts). The administration of a "scavenger" of hydroxyl radical, N-(2-mercaptopropionyl)-glycine (2 mM), decreased infarct size in an extent similar to that of cariporide (18+/-3%). The combination cariporide+N-(2-mercaptopropionyl)-glycine did not produce additional protection (17+/-1.7%). Each intervention [HOE 642 or N-(2-mercaptopropionyl)-glycine] and its combination improved the postischemic recovery of myocardial systolic and diastolic functions in a similar extent. The content of the thiobarbituric reactive substances of untreated hearts (1012+/-144 nmol/g) decreased to 431+/-81, 390+/-82, and 433+/-41 after cariporide, N-(2-mercaptopropionyl)-glycine, and cariporide+N-(2-mercaptopropionyl)-glycine treatments, respectively.
The present data support the conclusion that the cardioprotective effect of cariporide is associated with diminution of oxidative stress.
再灌注开始时会发生活性氧的爆发以及钠氢交换体的激活。本研究的目的是评估钠氢交换体抑制与活性氧之间关于心肌梗死面积测定的可能相互关系。
将离体大鼠心脏进行40分钟的冠状动脉阻塞和2小时的再灌注。通过氯化三苯基四氮唑染色技术测定梗死面积，并表示为危险区域的百分比。脂质过氧化作为氧化应激的标志物，通过硫代巴比妥反应性物质的浓度进行评估。
在再灌注的最初20分钟用钠氢交换体1亚型的选择性抑制剂HOE 642（卡里波罗；10微摩尔）进行处理，可显著减小梗死面积（未处理心脏为31±2%，处理后为15.1±2.4%）。给予羟自由基“清除剂”N-（2-巯基丙酰基）-甘氨酸（2毫摩尔）可使梗死面积减小程度与卡里波罗相似（18±3%）。卡里波罗+N-（2-巯基丙酰基）-甘氨酸联合使用未产生额外的保护作用（17±1.7%）。每种干预措施[HOE 642或N-（2-巯基丙酰基）-甘氨酸]及其联合使用在相似程度上改善了心肌收缩和舒张功能的缺血后恢复。未处理心脏的硫代巴比妥反应性物质含量（1012±144纳摩尔/克）在卡里波罗、N-（2-巯基丙酰基）-甘氨酸和卡里波罗+N-（2-巯基丙酰基）-甘氨酸处理后分别降至431±81、390±82和433±41。
目前的数据支持卡里波罗的心脏保护作用与氧化应激减轻相关的结论。
