SIALYL LEWIS(X)-CONTAINING OLIGOSACCHARIDE ATTENUATES MYOCARDIAL REPERFUSION INJURY IN CATS
SIALYL LEWIS(X)-CONTAINING OLIGOSACCHARIDE ATTENUATES MYOCARDIAL REPERFUSION INJURY IN CATS
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DOI：
10.1172/jci117066
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发表时间：
1994-03-01
影响因子：
15.9
通讯作者：
LEFER, AM
中科院分区：
文献类型：
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作者：
BUERKE, M;WEYRICH, AS;LEFER, AM
中性粒细胞（PMN）粘附于血管内皮是心肌再灌注损伤的重要机制。粘附过程最初由选择素介导（例如，P-和L-选择素）和针对这些粘附分子的单克隆抗体在缺血/再灌注模型中发挥心脏保护活性。这些选择素的反受体被认为是含碳水化合物的部分。在这方面，我们研究了可溶性含唾液酸刘易斯（x）寡糖（SLe（x）-OS）对猫心肌缺血/再灌注（MI/R）模型中PMN-内皮细胞相互作用的影响。在再灌注前10分钟给予SLe（x）-OS（10 mg/kg），再灌注后270分钟与其载体相比显著减少心肌坏死（6 +/- 1% vs. 35 +/- 4%的风险面积，P < 0.01）。与溶剂处理的猫相比，SLe（x）-OS中的血浆肌酸激酶活性显著降低，证实了心脏保护作用（P < 0.01）。接受SLe（x）-OS的猫的心脏收缩力（dP/dt max）在270分钟的R后显著保持（初始的97 +/- 2%对78 +/- 5%，P < 0.01）。此外，从接受SLe（x）-OS治疗的MI/R猫中分离的冠状动脉环中，对乙酰胆碱的内皮依赖性舒张作用显着保留（73 +/- 7% vs. 22 +/- 6%血管舒张，P < 0.01）。与溶剂组相比，Sle（x）-OS治疗组在270 min的R后，PR对冠状动脉血管内皮的粘附作用明显减弱（14 +/- 5 vs. 91 +/- 12 PMN/mm（2），P < 0.01）。我们的研究结果表明，SLe（x）-OS在MI/R后具有心脏保护作用并保留冠状动脉内皮功能，表明sialyl刘易斯（x）在心肌缺血/再灌注中PR-IN积累、内皮功能障碍和心肌损伤中的重要作用。
Neutrophil(PMN) adhesion to the vascular endothelium is an important mechanism of myocardial reperfusion injury. The adhesion process is initially mediated by selectins (e.g., P- and L-selectin), and monoclonal antibodies directed against these adhesion molecules exert cardioprotective activity in ischemia/reperfusion models. The counterreceptors for these selectins are thought to be carbohydrate-containing moieties. In this connection, we studied the effect of a soluble sialyl Lewis(x)-containing oligosaccharide (SLe(x)-OS) on PMN-endothelial interactions in a feline model of myocardial ischemia/reperfusion (MI/R). SLe(x)-OS (10 mg/kg), administered 10 min before R, significantly reduced myocardial necrosis compared with its vehicle 270 min after reperfusion (6 +/- 1% vs. 35 +/- 4% of area at risk, P < 0.01). The cardioprotection was confirmed by significantly lower plasma creatine kinase activities in SLe(x)-OS vs. vehicle-treated cats (P < 0.01). Cardiac contractility (dP/dt max) of cats receiving SLe(x)-OS was significantly preserved after 270 min of R (97 +/- 2% vs. 78 +/- 5% of initial, P < 0.01). Furthermore, endothelium-dependent relaxation to acetylcholine in coronary artery rings isolated from MI/R cats treated with SLe(x)-OS was significantly preserved (73 +/- 7% vs. 22 +/- 6% vasorelaxation, P < 0.01). In vitro PR adherence to coronary vascular endothelium after 270 min of R was significantly attenuated in the SLe(x)-OS-treated group compared with the vehicle group (14 +/- 5 vs. 91 +/- 12 PMN/mm(2), P < 0.01). Our results indicate that a SLe(x)-OS is cardioprotective and preserves coronary endothelial function after MI/R, indicating an important role of sialyl Lewis(x) in PR-IN accumulation, endothelial dysfunction, and myocardial injury in myocardial ischemia/reperfusion.