Hoffmeyer M R, Scalia R, Ross C R, Jones S P, Lefer D J
Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130, USA.
Am J Physiol Heart Circ Physiol. 2000 Dec;279(6):H2824-8. doi: 10.1152/ajpheart.2000.279.6.H2824.
We investigated the effects of PR-39, a recently discovered neutrophil inhibitor, in a murine model of myocardial ischemia-reperfusion injury. Mice were given an intravenous injection of vehicle (n = 12) or PR-39 (n = 9) and subjected to 30 min of coronary artery occlusion followed by 24 h of reperfusion. In addition, the effects of PR-39 on leukocyte rolling and adhesion were studied utilizing intravital microscopy of the rat mesentery. The area-at-risk per left ventricle was similar in vehicle- and PR-39-treated mice. However, myocardial infarct per risk area was significantly (P < 0.01) reduced in PR-39 treated hearts (21.0 +/- 3.8%) compared with vehicle (47.1 +/- 4.8%). Histological analysis of ischemic reperfused myocardium demonstrated a significant (P < 0.01) reduction in polymorphonuclear neutrophil (PMN) accumulation in PR-39-treated hearts (n = 6, 34.3 +/- 1.7 PMN/mm(2)) compared with vehicle-treated myocardium (n = 6, 59.7 +/- 3.1 PMN/mm(2)). In addition, PR-39 significantly (P < 0.05) attenuated leukocyte rolling and adherence in rat inflamed mesentery. These results indicate that PR-39 inhibits leukocyte recruitment into inflamed tissue and attenuated myocardial reperfusion injury in a murine model of myocardial ischemia-reperfusion.
我们在小鼠心肌缺血再灌注损伤模型中研究了最近发现的中性粒细胞抑制剂PR - 39的作用。给小鼠静脉注射赋形剂（n = 12）或PR - 39（n = 9），然后进行30分钟冠状动脉闭塞，随后再灌注24小时。此外，利用大鼠肠系膜活体显微镜研究了PR - 39对白细胞滚动和黏附的影响。接受赋形剂和PR - 39治疗的小鼠左心室危险区域面积相似。然而，与赋形剂组（47.1 +/- 4.8%）相比，PR - 39治疗组心脏的每危险区域心肌梗死面积显著降低（P < 0.01）（21.0 +/- 3.8%）。对缺血再灌注心肌的组织学分析表明，与赋形剂治疗的心肌（n = 6，59.7 +/- 3.1个多形核中性粒细胞/mm²）相比，PR - 39治疗组心脏（n = 6，34.3 +/- 1.7个多形核中性粒细胞/mm²）中多形核中性粒细胞（PMN）的积聚显著减少（P < 0.01）。此外，PR - 39显著（P < 0.05）减弱了大鼠炎症肠系膜中的白细胞滚动和黏附。这些结果表明，在小鼠心肌缺血再灌注模型中，PR - 39可抑制白细胞募集到炎症组织中，并减轻心肌再灌注损伤。
