Han Jingyan, Shuvaev Vladimir V, Muzykantov Vladimir R
Institute for Translational Medicine & Therapeutics & Department of Pharmacology, University of Pennsylvania School of Medicine, TRC 10-125, 3400 Civic Center Blvd, Bldg 421, Philadelphia, PA 19104-5158, USA.
Ther Deliv. 2012 Feb;3(2):263-76. doi: 10.4155/tde.11.151.
Reactive oxygen species (ROS) are implicated as injurious and as signaling agents in human maladies including inflammation, hyperoxia, ischemia-reperfusion and acute lung injury. ROS produced by the endothelium play an important role in vascular pathology. They quench, for example, nitric oxide, and mediate pro-inflammatory signaling. Antioxidant interventions targeted for the vascular endothelium may help to control these mechanisms. Animal studies have demonstrated superiority of targeting ROS-quenching enzymes catalase and superoxide dismutase to endothelial cells over nontargeted formulations. A diverse arsenal of targeted antioxidant formulations devised in the last decade shows promising results for specific quenching of endothelial ROS. In addition to alleviation of toxic effects of excessive ROS, these targeted interventions suppress pro-inflammatory mechanisms, including endothelial cytokine activation and barrier disruption. These interventions may prove useful in experimental biomedicine and, perhaps, in translational medicine.
活性氧(ROS)在包括炎症、高氧、缺血再灌注和急性肺损伤在内的人类疾病中被认为是有害因子和信号传导介质。内皮细胞产生的ROS在血管病理学中起重要作用。例如,它们会淬灭一氧化氮,并介导促炎信号传导。针对血管内皮的抗氧化干预措施可能有助于控制这些机制。动物研究表明,将ROS淬灭酶过氧化氢酶和超氧化物歧化酶靶向内皮细胞比非靶向制剂更具优势。在过去十年中设计出的各种靶向抗氧化制剂,在特异性淬灭内皮细胞ROS方面显示出了有前景的结果。除了减轻过量ROS的毒性作用外,这些靶向干预措施还能抑制促炎机制,包括内皮细胞因子激活和屏障破坏。这些干预措施可能在实验生物医学中,也许在转化医学中证明是有用的。