氧自由基及清除剂对缺血再灌注期间心脏细胞外胶原基质的影响。

Effects of oxygen free radicals and scavengers on the cardiac extracellular collagen matrix during ischemia-reperfusion.

作者信息

Lonn E, Factor S M, Van Hoeven K H, Wen W H, Zhao M, Dawood F, Liu P

机构信息

Centre for Cardiovascular Research, University of Toronto, Ontario.

出版信息

Can J Cardiol. 1994 Mar;10(2):203-13.

PMID:8143221

Abstract

OBJECTIVE

Collagen is lysed early during ischemia-reperfusion, but whether this is due to ischemia or reperfusion injury is not known. The effect of oxygen free radicals and free radical scavengers on left ventricular hemodynamics, myocardial morphology and collagen content were studied in an isolated, Langendorff-perfused rat heart model of regional ischemia-reperfusion.

METHODS

All hearts received left anterior descending coronary artery ischemia for 20 mins. Group 1 had ischemia only; group 2 had ischemia followed by reperfusion with oxygenated Krebs-Henseleit buffer for 20 mins; group 3 had oxygen free radicals generated by hypoxanthine and xanthine oxidase during reperfusion; group 4 had free radical scavengers with superoxide dismutase plus catalase; group 5 had both oxygen free radicals and free radical scavengers during reperfusion.

RESULTS

Left ventricular developed pressure decreased significantly in group 3 during ischemia followed by reperfusion (58 +/- 3.1 mmHg versus 42 +/- 2.4 mmHg, P = 0.004), but did not change significantly in any of the other groups. Necrosis score on pathology was highest in group 3; this score also was higher than that in group 5 with free radical scavengers added (3.0 +/- 0.3 versus 2.0 +/- 0.4, P = 0.07) and higher than that of group 2 with reperfusion with buffer only (3.0 +/- 0.3 versus 1.4 +/- 0.5, P < 0.05). Collagen content decreased significantly compared with control in group 3 only with ischemia followed by reperfusion with the addition of oxygen free radicals (18.4 +/- 1.5 versus 11.9 +/- 1.7 g/mg protein, P < 0.05). The addition of free radical scavengers in group 5 mainly attenuated the collagen loss. Scanning electron microscopy revealed profound structural changes of the extracellular collagen matrix in numerous regions of 'stunning' independent of tissue necrosis.

CONCLUSIONS

We conclude that: first, oxygen free radicals trigger significant collagen damage and left ventricular dysfunction during reperfusion; second, these changes extend beyond the ischemic damage alone; and third, free radical scavengers can effectively limit oxygen free radical-induced collagen loss and left ventricular dysfunction.

摘要

目的

胶原蛋白在缺血再灌注早期会被分解，但这是由于缺血损伤还是再灌注损伤尚不清楚。在离体的、采用Langendorff灌注的大鼠局部缺血再灌注心脏模型中，研究了氧自由基和自由基清除剂对左心室血流动力学、心肌形态及胶原蛋白含量的影响。

方法

所有心脏均接受左冠状动脉前降支缺血20分钟。第1组仅进行缺血处理；第2组缺血后用充氧的Krebs-Henseleit缓冲液再灌注20分钟；第3组在再灌注期间用次黄嘌呤和黄嘌呤氧化酶产生氧自由基；第4组用超氧化物歧化酶加过氧化氢酶作为自由基清除剂；第5组在再灌注期间既有氧自由基又有自由基清除剂。

结果

在第3组中，缺血后再灌注期间左心室舒张末压显著降低（58±3.1 mmHg对42±2.4 mmHg，P = 0.004），但其他组均无显著变化。病理学上的坏死评分在第3组中最高；该评分也高于添加了自由基清除剂的第5组（3.0±0.3对2.0±0.4，P = 0.07），且高于仅用缓冲液再灌注的第2组（3.0±0.3对1.4±0.5，P < 0.05）。仅在第3组中，缺血后再灌注并添加氧自由基时，胶原蛋白含量与对照组相比显著降低（18.4±1.5对11.9±1.7 g/mg蛋白质，P < 0.05）。第5组中添加自由基清除剂主要减轻了胶原蛋白的损失。扫描电子显微镜显示，在许多“顿抑”区域，细胞外胶原蛋白基质有明显的结构变化，且与组织坏死无关。