GLYCOCALYX PROTECTION REDUCES LEUKOCYTE ADHESION AFTER ISCHEMIA/REPERFUSION
GLYCOCALYX PROTECTION REDUCES LEUKOCYTE ADHESION AFTER ISCHEMIA/REPERFUSION
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DOI：
10.1097/shk.0b013e3181cdc363
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发表时间：
2010-08-01
期刊：
影响因子：
3.1
通讯作者：
Becker, Bernhard F.
中科院分区：
文献类型：
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作者：
Chappell, Daniel;Doerfler, Nina;Becker, Bernhard F.
多形核中性粒细胞（PMN）与冠状动脉内皮细胞的粘附是心肌缺血/再灌注损伤的关键事件。粘附分子通常隐藏在糖萼内，覆盖每个健康的血管内皮，但因缺血/再灌注而脱落。我们的目的是显示是否保护的糖萼无论是氢化可的松或抗凝血酶可以减少缺血后白细胞粘附。用Krebs-Henseleit缓冲液灌注的离体豚鼠心脏在不存在或存在氢化可的松（10 μ g/mL）或抗凝血酶（1U/mL）的情况下经受20分钟的温热（37 ℃）无血流缺血和连续10分钟的再灌注。在再灌注结束时冠状动脉内注射3 × 10（6）PMN，但事先不接触药物。根据冠状动脉细胞输入和输出之间的差异计算PMN的隔离。在冠状动脉通过前后检测PMN上整合素CD 11b的表达。缺血/再灌注诱导糖萼严重降解（冠状静脉syndecan-1释放，171 +/- 15 ng/g心脏vs.基础，19 +/- 2 ng/g;硫酸乙酰肝素，5.27 +/- 0.28 μ g/g vs.基础，0.26 +/- 0.06 μ g/g）和增加的PMN粘附（38.1% +/- 3.5% vs.基础，11.7% +/- 3.1%）。氢化可的松和抗凝血酶不仅能减少糖萼脱落（syndecan-1释放，34 +/- 6 ng/g和26 +/- 5 ng/g;硫酸乙酰肝素，分别为1.96 +/- 0.24 μ g/g和1.28 +/- 0.2 μ g/g），但也有PMN粘附（分别为17.3% +/- 2.2%和25.4% +/-3.3%）。电子显微镜检查显示，大部分完整的冠状动脉糖萼预处理后，任何一种药物。PMN在冠状动脉通过时的激活不受影响。糖萼的保存减轻了缺血后PMN的粘附。因此，用氢化可的松或抗凝血酶进行预处理可以减轻血管渗漏、组织水肿和炎症。
Adhesion of polymorphonuclear neutrophils (PMN) to coronary endothelium is a key event for cardiac ischemia/reperfusion injury. Adhesion molecules are normally harbored within the glycocalyx, clothing every healthy vascular endothelium, but shed by ischemia/reperfusion. Our aim was to show whether protection of the glycocalyx with either hydrocortisone or antithrombin can reduce postischemic leukocyte adhesion. Isolated guinea pig hearts, perfused with Krebs-Henseleit buffer, were subjected to 20 min of warm (37 degrees C) no-flow ischemia and consecutive 10 min of reperfusion, either in the absence or presence of hydrocortisone (10 mu g/mL) or antithrombin (1 U/mL). An intracoronary bolus of 3 x 10(6) PMN was applied at the end of reperfusion but without prior contact to the drugs. The sequestration of PMN was calculated from the difference between coronary input and output of cells. Expression of the integrin CD11b on PMN was measured before and after coronary passage. Ischemia/reperfusion induced severe degradation of the glycocalyx (coronary venous syndecan-1 release, 171 +/- 15 ng/g heart vs. basal, 19 +/- 2 ng/g; heparan sulfate, 5.27 +/- 0.28 mu g/g vs. basal, 0.26 +/- 0.06 mu g/g) and increased PMN adhesion (38.1% +/- 3.5% vs. basal, 11.7% +/- 3.1%). Hydrocortisone and antithrombin both not only reduced glycocalyx shedding (syndecan-1 release, 34 +/- 6 ng/g and 26 +/- 5 ng/g; heparan sulfate, 1.96 +/- 0.24 mu g/g and 1.28 +/- 0.2 mu g/g, respectively), but also PMN adhesion (17.3% +/- 2.2% and 25.4% +/- 3.3%, respectively) after ischemia/reperfusion. Electron microscopy revealed a mostly intact coronary glycocalyx after pretreatment with either drug. Activation of PMN upon coronary passage was not influenced. Preservation of the glycocalyx mitigates postischemic PMN adhesion. Preconditioning with either hydrocortisone or antithrombin should, thus, alleviate vascular leakage, tissue edema, and inflammation.