Kim C H, Choi H, Chun Y S, Kim G T, Park J W, Kim M S
Department of Pharmacology and BK21 Human Life Sciences, Seoul National University College of Medicine and Heart Research Institute SNUMRC, South Korea.
Pflugers Arch. 2001 Jul;442(4):519-25. doi: 10.1007/s004240100571.
Ischemia-reperfusion injury is a major complication occurring in heart stroke, cardiopulmonary bypass surgeries, and heart transplantation. Reactive oxygen species generated during the reperfusion phase overwhelm the scavenging capacities of antioxidant enzymes, and result in oxidative damage to the myocardium. We examined whether hyperbaric oxygenation (HBO) pretreatment induces antioxidant enzymes and protects the heart from subsequent ischemia-reperfusion injury. Rats were intermittently exposed to 100% O2 at 3 ATA (where ATA is absolute atmosphere) for 1 h daily and then sacrificed after 24 h of recovery in room air. Isolated hearts were subjected to 40 min of ischemia and 90 min of reperfusion. HBO pretreatment was found to condition the heart and enhance enzymatic activity and gene expression of catalase, thereby significantly reducing infarct size after reperfusion. A catalase inhibitor, 3-amino-1,2,4-triazole, completely abolished the infarct-limiting effect of HBO pretreatment, which suggests that HBO-induced tolerance against ischemia-reperfusion injury is due to catalase induction. Our results imply that HBO preconditioning may be developed as a new preventive measure for reperfusion injury in the heart.
缺血再灌注损伤是发生在心脏中风、体外循环手术和心脏移植中的一种主要并发症。再灌注阶段产生的活性氧超过了抗氧化酶的清除能力,导致心肌发生氧化损伤。我们研究了高压氧(HBO)预处理是否能诱导抗氧化酶并保护心脏免受随后的缺血再灌注损伤。大鼠每天在3个绝对大气压(ATA,其中ATA为绝对大气压)下间歇性暴露于100%氧气中1小时,然后在室内空气中恢复24小时后处死。分离的心脏进行40分钟的缺血和90分钟的再灌注。发现HBO预处理可使心脏适应并增强过氧化氢酶的酶活性和基因表达,从而显著减小再灌注后的梗死面积。过氧化氢酶抑制剂3-氨基-1,2,4-三唑完全消除了HBO预处理的梗死限制作用,这表明HBO诱导的对缺血再灌注损伤的耐受性是由于过氧化氢酶的诱导。我们的结果表明,HBO预处理可能被开发为一种预防心脏再灌注损伤的新措施。