Reactive oxygen species mediate modification of glycocalyx during ischemia-reperfusion injury
Reactive oxygen species mediate modification of glycocalyx during ischemia-reperfusion injury
复制标题
DOI：
10.1152/ajpheart.00796.2005
复制
发表时间：
2006-06-01
影响因子：
4.8
通讯作者：
Duling, Brian R.
中科院分区：
文献类型：
--
作者：
Rubio-Gayosso, Ivan;Platts, Steven H.;Duling, Brian R.
糖萼(Gcx)是一种复杂且鲜为人知的结构，覆盖于内皮细胞的管腔表面。已知它是血管流变学和通透性的决定因素，可能是缺血再灌注(I/R)引起的血管损伤的关键控制点。我们用活体显微镜观察了I/R损伤对小鼠微血管Gcx两种特性的影响：大分子(阴离子-右旋糖苷)的排斥和红细胞(RBC)的毛细血管内分布。在该模型中，Gcx被I/R损伤迅速修饰，70 kDa阴离子-葡聚糖穿透增加，而对580 kDa阴离子-右旋糖苷的穿透或RBC排斥无明显影响。I/R损伤的影响似乎是通过迅速产生活性氧物种(ROS)来调节的，因为外源超氧化物歧化酶-过氧化氢酶的加入可以改善这些ROS。静脉应用别嘌醇或肝素也可抑制I/R损伤的影响，我们将别嘌醇的疗效解释为黄嘌呤氧化还原酶(XOR)在I/R损伤反应中的作用的证据。肝素被认为取代了Gcx中肝素结合区的XOR，减少了I/R的影响。外源性透明质酸血管内注射也部分防止或完全逆转了I/R损伤的影响。这些数据表明：1)Gcx在I/R损伤中的易感性；2)局部产生的ROS在Gcx损伤中的重要性；以及3)肝素结合位点在调节ROS产生中的潜在重要性。我们的发现进一步强调了糖胺多聚糖与体内Gcx的病理生理学之间的关系。
The glycocalyx (Gcx) is a complex and poorly understood structure covering the luminal surface of endothelial cells. It is known to be a determinant of vascular rheology and permeability and may be a key control site for the vascular injuries caused by ischemia-reperfusion (I/R). We used intravital-microscopy to evaluate the effects of I/R injury on two properties of Gcx in mouse cremasteric microvessels: exclusion of macromolecules (anionic-dextrans) and intracapillary distribution of red blood cells (RBC). In this model, the Gcx is rapidly modified by I/R injury with an increase in 70-kDa anionic-dextran penetration without measurable effect on the penetration of 580-kDa anionic-dextran or on RBC exclusion. The effects of I/R injury appear to be mediated by the rapid production of reactive oxygen species (ROS) because they are ameliorated by the addition of exogenous superoxide dismutase-catalase. Intravenous application of allopurinol or heparin also inhibited the effects of I/R injury, and we interpret efficacy of allopurinol as evidence for a role for xanthine-oxidoreductase (XOR) in the response to I/R injury. Heparin, which is hypothesized to displace XOR from a heparin-binding domain in the Gcx, reduced the effects of I/R. The effects of I/R injury were also partially prevented or fully reversed by the intravascular infusion of exogenous hyaluronan. These data demonstrate: 1) the liability of Gcx during I/R injury; 2) the importance of locally produced ROS in the injury to Gcx; and 3) the potential importance of heparin-binding sites in modulating the ROS production. Our findings further highlight the relations between glycosaminoglycans and the pathophysiology of Gcx in vivo.