Departamento de Bioquímica, Instituto Nacional de Cardiología, Ignacio Chávez, Juan Badiano No. 1. Colonia Sección XVI, 14080 México, Distrito Federal.
Exp Physiol. 2012 Oct;97(10):1119-30. doi: 10.1113/expphysiol.2012.065763. Epub 2012 May 4.
Oxidant stress, among other effectors, is implicated in the sequel of myocardial reperfusion injury. It is generally accepted that maintaining the balance between oxidant and antioxidant signalling within the cell provides protection against reperfusion damage. The cardioprotective strategy of postconditioning (PC) reduces reperfusion injury through complex mechanisms; however, the contribution of the antioxidant system has not been fully investigated. In this study, isolated rat hearts were subjected to PC after 30 min global ischaemia, and then to 5 min (IR5) or 60 min of reperfusion (IR60). Postconditioning significantly increased the left ventricular developed pressure and the double product (heart rate × left ventricular developed pressure) for both early (PC5) and prolonged reperfusion (PC60, PC before 60 min of reperfusion). Necrotic tissue diminished to 10.8% in PC60 hearts, compared with 49% of infarct size measured in IR60 hearts (P < 0.05 versus IR60). Also, protein carbonylation and malondialdehyde levels decreased and were correlated with a significant augmentation in CuZn superoxide dismutase activity (P < 0.05, PC60 versus IR60) and increased glutathione redox state (GSH:GSSG ratio; P < 0.05, PC60 versus IR60). Diethylthiocarbamate, a non-selective superoxide dismutase inhibitor, significantly diminished the protection afforded by PC when administered throughout the protocol. However, administration of this inhibitor only during reperfusion had no effect on PC-induced cardioprotection. These results indicate that non-enzymatic antioxidants account for the protective effect of PC, modifying the oxidant stress caused by ischaemic reperfusion in rats. The contribution of CuZn superoxide dismutase activity in the observed cardioprotective effect is less clear, and could be relevant if acting in concert with other PC-activated mechanisms.
氧化应激等效应因子与心肌再灌注损伤的发生有关。一般认为，维持细胞内氧化还原信号的平衡可以提供对再灌注损伤的保护。后处理（PC）的心脏保护策略通过复杂的机制减少再灌注损伤；然而，抗氧化系统的贡献尚未得到充分研究。在这项研究中，离体大鼠心脏在 30 分钟的整体缺血后进行 PC，然后进行 5 分钟（IR5）或 60 分钟的再灌注（IR60）。PC 显著增加了左心室发展压和双乘积（心率×左心室发展压），无论是早期（PC5）还是延长的再灌注（PC60，PC 之前 60 分钟的再灌注）。与 IR60 心脏（PC60 心脏为 10.8%，IR60 心脏为 49%）相比，PC60 心脏的坏死组织减少了 49%。此外，蛋白质羰基化和丙二醛水平降低，并与 CuZn 超氧化物歧化酶活性的显著增加相关（P<0.05，PC60 与 IR60 相比）和增加的谷胱甘肽氧化还原状态（GSH：GSSG 比；P<0.05，PC60 与 IR60 相比）。二乙基二硫代氨基甲酸盐，一种非选择性超氧化物歧化酶抑制剂，在整个方案中给药时显著降低了 PC 提供的保护作用。然而，在再灌注期间仅给予该抑制剂对 PC 诱导的心脏保护没有影响。这些结果表明，非酶抗氧化剂解释了 PC 的保护作用，改变了大鼠缺血再灌注引起的氧化应激。CuZn 超氧化物歧化酶活性在观察到的心脏保护作用中的贡献不太清楚，如果与其他 PC 激活机制协同作用，可能会相关。
