Endothelial cell protection against ischemia/reperfusion injury by lecithinized superoxide dismutase
Endothelial cell protection against ischemia/reperfusion injury by lecithinized superoxide dismutase
复制标题
DOI：
10.1046/j.1523-1755.2001.060002786.x
复制
发表时间：
2001-08-01
影响因子：
19.6
通讯作者：
Fuggle, SV
中科院分区：
文献类型：
--
作者：
Koo, DDH;Welsh, KI;Fuggle, SV
背景用于移植的器官可能会经历长时间的冷缺血保存，从而导致氧自由基介导的再灌注损伤。卵磷脂化超氧化物歧化酶(Lec-SOD)是一种新型的自由基清除剂，与细胞膜具有很高的亲和力。本研究的目的是确定在器官保存条件下，Lec-SOD是否与内皮细胞结合，直接介导内皮细胞表面的抗氧化活性，从而提供对缺血/再灌注损伤的保护作用。对大血管内皮细胞(HUVEC)和人微血管内皮细胞系HMEC-1进行了体外研究。目的：探讨在器官保存液中加入Lec-SOD的潜在治疗效果。建立了冷缺氧/复氧系统，以检测Lec-SOD与内皮细胞的结合亲和力，从而保护内皮细胞免受缺氧/复氧诱导的细胞死亡。中性粒细胞粘连。LEC-SOD与内皮细胞的亲和力高于未修饰的重组人超氧化物歧化酶(RhSOD)，并能显著保护HUVEC和HMEC-1免受冷缺氧27小时后的细胞死亡(P<；0.01)。此外，Lec-SOD可显著抑制缺氧和复氧刺激的中性粒细胞与内皮细胞的黏附，而卵磷脂和重组人超氧化物歧化酶对此无明显影响(P0.01)。流式细胞仪分析显示缺氧/复氧可上调E-选择素和ICAM-1的表达，而低氧/复氧可部分抑制E-选择素和ICAM-1的表达。本研究结果提示，在器官保存液中加入Lec-SOD对移植后内皮细胞的冷缺血再灌注损伤具有有效的保护作用。
Background Organs used for transplantation may experience long periods of cold ischemic preservation and consequently oxygen free radical-mediated damage following reperfusion. Lecithinized superoxide dismutase (lec-SOD) is a novel Free radical scavenger that has been shown to bind with high affinity to cell membranes. The aim of this study was to determine whether lec-SOD bound to endothelial cells under organ preservation conditions to mediate direct antioxidant activity at the endothelial cell surface and thus offer protection against the harmful effects of ischemia/reperfusion injury.Methods. An in vitro study was performed on large vessel endothelial cells (HUVEC) and a human microvascular endothelial cell line HMEC-1. to investigate the potential therapeutic benefits of incorporating lec-SOD into organ preservation solution. A cold hypoxia/reoxygenation system was developed to examine lec-SOD binding affinity to endothelial cells, protection against hypoxia/reoxgenation-induced cell death. and neutrophil adhesion.Results. Lec-SOD bound to endothelial cells with higher affinity than unmodified recombinant human superoxide dismutase (rhSOD) and significantly protected both HUVEC and HMEC-1 from cell death following 27 hours of cold hypoxia (P < 0.01). Furthermore, neutrophil adhesion to the endothelium stimulated by hypoxia a < nd reoxygenation was significantly inhibited by treatment with lec-SOD but not by lecithin or rhSOD (P 0.01). Analysis by flow cytometry demonstrated that E-selectin and ICAM-1 were up-regulated by hypoxia/reoxygenation that was inhibited in part by lec-SOD.Conclusions. The results from this study suggest that incorporation of lec-SOD into organ preservation solutions provides effective protection to endothelial cells against cold ischemia and reperfusion injury following transplantation.