Superoxide dismutase and N-2-mercaptopropionyl glycine attenuate infarct size limitation effect of ischaemic preconditioning in the rabbit.
Superoxide dismutase and N-2-mercaptopropionyl glycine attenuate infarct size limitation effect of ischaemic preconditioning in the rabbit.
复制标题
超氧化物歧化酶和 N-2-巯基丙酰甘氨酸可减弱兔缺血预处理对梗死面积的限制作用。
作者：
Masaru Tanaka;Hisayoshi Fujiwara;K. Yamasaki;S. Sasayama
客观化
缺血预适应可能是由预适应过程中产生的氧自由基介导的。关于超氧化物歧化酶(SOD)在减弱预适应的心脏保护作用方面的作用，已有相互矛盾的结果报道。这项研究的目的是通过检测三种不同的氧自由基清除剂对预适应限制心肌梗死面积的作用来调和这一冲突。
方法
麻醉开胸兔冠状动脉阻断30min，再灌注48h。在预适应组，兔在持续缺血30min之前，单次阻断5min，再灌注5min。在这些组中，在预适应前和预适应期间，注入氧自由基清除剂超氧化物歧化酶(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。在非预适应组，这些药物在缺血30分钟前的相同时间段内给药。再灌流2d后，显微镜下测量心肌梗死面积。
结果
在生理盐水对照组，预适应明显地限制了显微镜下的梗塞面积(危险区域的百分比)：13(SEM3)%(n=9)v49(9)%(n=8)，p<；0.05。心肌梗死面积分别为31(5)%(n=11)和42(8)%(n=11)，而丹参酮治疗组[心肌梗死面积为23(6)%(n=11)，生理盐水预适应组与生理盐水预适应组]无明显差异。非预适应组大鼠脑梗塞面积分别为50(9)%(n=7)、56(5)%(n=8)和61(6)%(n=8)，P=生理盐水对照组。
结论
预适应的心脏保护作用至少部分是由氧自由基介导的，而氧自由基可被兔体内的超氧化物歧化酶或MPG清除。
OBJECTIVE
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
Cardioprotection by preconditioning is mediated, at least in part, by oxyradicals which are scavenged by SOD or MPG in rabbits.