Tanaka M, Fujiwara H, Yamasaki K, Sasayama S
Third Division of Medicine, Kyoto University, Japan.
Cardiovasc Res. 1994 Jul;28(7):980-6. doi: 10.1093/cvr/28.7.980.
Ischaemic preconditioning may be mediated by oxygen free radicals generated during preconditioning. Conflicting results have been reported regarding the effect of superoxide dismutase (SOD) in attenuating the cardioprotective effect of preconditioning. The aim of the study was to reconcile this conflict by examining the effect of three different oxyradical scavengers on the infarct size limiting effect of preconditioning.
Anaesthetised open chest rabbits were subjected to 30 min coronary occlusion and 48 h reperfusion. In the preconditioning groups, rabbits were subjected to a single 5 min occlusion and 5 min reperfusion before 30 min sustained ischaemia. In these groups, the oxyradical scavengers SOD (15,000 U.kg-1), N-2-mercaptopropionyl glycine (MPG, 20 mg.kg-1), and dimethylthiourea (DMTU, 500 mg.kg-1), or placebo saline, were infused before and during preconditioning. In the non-preconditioning groups, these agents were given in the same time frame before 30 min of ischaemia. After 2 d reperfusion, infarct size was measured microscopically.
In the saline treated controls, preconditioning markedly limited microscopical infarct size (percent of area at risk): 13(SEM 3)% (n = 9) v 49(9)% (n = 8), p < 0.05. Treatment of the preconditioning groups with SOD or MPG attenuated this cardioprotection [infarct size 31(5)% (n = 11) and 42(8)% (n = 11), respectively, p < 0.05 v the saline treated preconditioning group], but treatment with DMTU did not [infarct size 23(6)% (n = 11), p = NS v the saline treated preconditioning group]. In the non-preconditioning groups, none of the treatments modified infarct size: 50(9)% (n = 7), 56(5)% (n = 8), and 61(6)%, (n = 8), respectively, p = NS v saline treated control.
Cardioprotection by preconditioning is mediated, at least in part, by oxyradicals which are scavenged by SOD or MPG in rabbits.
缺血预处理可能由预处理过程中产生的氧自由基介导。关于超氧化物歧化酶（SOD）在减弱预处理的心脏保护作用方面的效果，已有相互矛盾的报道。本研究的目的是通过检测三种不同的氧自由基清除剂对预处理梗死面积限制作用的影响来调和这一矛盾。
对麻醉开胸的兔子进行30分钟冠状动脉闭塞和48小时再灌注。在预处理组中，兔子在30分钟持续性缺血前先经历一次5分钟闭塞和5分钟再灌注。在这些组中，在预处理前和预处理期间输注氧自由基清除剂SOD（15,000 U.kg-1）、N-2-巯基丙酰甘氨酸（MPG，20 mg.kg-1）和二甲基硫脲（DMTU，500 mg.kg-1），或安慰剂生理盐水。在非预处理组中，在30分钟缺血前的相同时间段给予这些药物。再灌注2天后，显微镜下测量梗死面积。
在生理盐水处理的对照组中，预处理显著限制了显微镜下的梗死面积（危险区域面积的百分比）：13（标准误3）%（n = 9）对比49（9）%（n = 8），p < 0.05。用SOD或MPG处理预处理组减弱了这种心脏保护作用[梗死面积分别为31（5）%（n = 11）和42（8）%（n = 11），p < 0.05对比生理盐水处理的预处理组]，但用DMTU处理则没有[梗死面积23（6）%（n = 11），p = 无显著性差异对比生理盐水处理的预处理组]。在非预处理组中，没有一种处理改变梗死面积：分别为50（9）%（n = 7）、56（5）%（n = 8）和61（6）%（n = 8），p = 无显著性差异对比生理盐水处理的对照组。
预处理的心脏保护作用至少部分由氧自由基介导，在兔子中这些氧自由基可被SOD或MPG清除。
