Scott G S, Hooper D C
Department of Microbiology and Immunology and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Med Hypotheses. 2001 Jan;56(1):95-100. doi: 10.1054/mehy.2000.1118.
Peroxynitrite, the product of the free radicals nitric oxide and superoxide, has been implicated in the pathogenesis of inflammatory CNS disorders. Uric acid, an effective scavenger of peroxynitrite, is a purine metabolite present at high levels in the serum of hominoids relative to lower-order animals due to the functional deletion of urate oxidase. Raising the normally low levels of uric acid in mice is therapeutic for experimental allergic encephalomyelitis, an animal model of multiple sclerosis. This therapeutic activity of uric acid is associated with the inhibition of peroxynitrite-induced tissue damage, blood-CNS barrier permeability changes, and CNS inflammation. Based on these findings we have concluded that peroxynitrite has an important role in promoting enhanced vascular permeability and inflammatory cell extravasation. We hypothesize that higher uric acid levels in hominoids evolved to protect against this process.
过氧亚硝酸盐是自由基一氧化氮和超氧化物的产物，与炎症性中枢神经系统疾病的发病机制有关。尿酸是过氧亚硝酸盐的有效清除剂，由于尿酸氧化酶功能缺失，相对于低等动物，尿酸作为嘌呤代谢产物在类人猿血清中含量较高。提高小鼠体内通常较低水平的尿酸对实验性变应性脑脊髓炎（一种多发性硬化症的动物模型）具有治疗作用。尿酸的这种治疗活性与抑制过氧亚硝酸盐诱导的组织损伤、血脑屏障通透性变化和中枢神经系统炎症有关。基于这些发现，我们得出结论，过氧亚硝酸盐在促进血管通透性增强和炎症细胞外渗方面具有重要作用。我们推测，类人猿体内较高的尿酸水平是为了抵御这一过程而进化形成的。
