Monoamine oxidase-induced hydroxyl radical production and cardiomyocyte injury during myocardial ischemia-reperfusion in rats
Monoamine oxidase-induced hydroxyl radical production and cardiomyocyte injury during myocardial ischemia-reperfusion in rats
复制标题
DOI：
10.3109/10715762.2016.1162300
复制
发表时间：
2016-01-01
影响因子：
3.3
通讯作者：
Shirai, Mikiyasu
中科院分区：
文献类型：
--
作者：
Inagaki, Tadakatsu;Akiyama, Tsuyoshi;Shirai, Mikiyasu
为阐明单胺氧化酶(MAO)在心肌缺血及再灌注损伤中的作用，我们将微透析技术应用于麻醉大鼠心脏。在诱导缺血30min和再灌流60min期间收集透析液样本。我们用捕捉剂(4-羟基苯甲酸)监测了透析液3，4-二氢苯甲酸(3，4-DHBA)浓度作为羟基自由基产生的指标，并监测了透析液中肌红蛋白浓度作为缺血区心肌细胞损伤的指标。研究了局部应用MAO抑制剂pargyline的效果。3，4-DHBA浓度从阻断前的1.9+/-0.5 nM上升到阻断后20-30分钟的3.5+/-0.7 nM。再灌流后，透析液3，4-DHBA浓度进一步升高，在再灌流后20~30min达到最大值(4.5+/-0.3 nM)，此后趋于稳定。Pargyline对3，4-DHBA浓度的平均抑制作用在阻断期间和再灌流期间分别达到72%和67%。透析液肌红蛋白浓度从阻断前的235+/-60 ng/ml上升到阻断后20-30分钟的1309+/-298 ng/ml。再灌流后，透析液中肌红蛋白浓度进一步升高，在再灌流后10~20min达到峰值(5833+/-1017 ng/ml)，然后下降。Pargyline使平均透析液肌红蛋白浓度在闭塞期间降低了56%，在再灌流期间降低了41%。MAO在缺血和再灌流过程中产生的羟基自由基和心肌细胞损伤中起重要作用。
To elucidate the involvement of monoamine oxidase (MAO) in hydroxyl radical production and cardiomyocyte injury during ischemia as well as after reperfusion, we applied microdialysis technique to the heart of anesthetized rats. Dialysate samples were collected during 30 min of induced ischemia followed by 60 min of reperfusion. We monitored dialysate 3,4-dihydrobenzoic acid (3,4-DHBA) concentration as an index of hydroxyl radical production using a trapping agent (4-hydroxybenzoic acid), and dialysate myoglobin concentration as an index of cardiomyocyte injury in the ischemic region. The effect of local administration of a MAO inhibitor, pargyline, was investigated. Dialysate 3,4-DHBA concentration increased from 1.9 +/- 0.5 nM at baseline to 3.5 +/- 0.7 nM at 20-30 min of occlusion. After reperfusion, dialysate 3,4-DHBA concentration further increased reaching a maximum (4.5 +/- 0.3 nM) at 20-30 min after reperfusion, and stabilized thereafter. Pargyline suppressed the averaged increase in dialysate 3,4-DHBA concentration by similar to 72% during occlusion and by similar to 67% during reperfusion. Dialysate myoglobin concentration increased from 235 +/- 60 ng/ml at baseline to 1309 +/- 298 ng/ml at 20-30 min after occlusion. After reperfusion, dialysate myoglobin concentration further increased reaching a peak (5833 +/- 1017 ng/ml) at 10-20 min after reperfusion, and then declined. Pargyline reduced the averaged dialysate myoglobin concentration by similar to 56% during occlusion and by similar to 41% during reperfusion. MAO plays a significant role in hydroxyl radical production and cardiomyocyte injury during ischemia as well as after reperfusion.