Nihei H, Kanemitsu H, Tamura A, Oka H, Sano K
Department of Neurosurgery, University of Virginia, Charlottesville.
Neurosurgery. 1989 Oct;25(4):613-7. doi: 10.1097/00006123-198910000-00016.
The existence of uric acid in mammalian brain was recently reported, but it has not yet become a consensus. The mammalian brain has been thought to lack xanthine oxidase, which catalyzes hypoxanthine to xanthine and xanthine to uric acid as the last steps of ATP degradation in other tissue. Using high-performance liquid chromatography, we performed assays for hypoxanthine, xanthine, and uric acid in rat brain after cerebral ischemia. It was confirmed that all three substances showed significant augmentation in the removed brains and that the chronological order of those increases corresponded to the order in the metabolic pathway. Allopurinol, a specific inhibitor of xanthine oxidase, significantly suppressed the increases in uric acid and xanthine, and a compensatory accumulation of hypoxanthine was observed. From these results, it was concluded that uric acid does exist in the brain, increases after ischemia, and is possibly the end product of purine degradation in the brain. Furthermore, it is suggested that xanthine oxidase exists in the brain and catalyzes the reaction from hypoxanthine to xanthine and then to uric acid. These reactions catalyzed by xanthine oxidase are considered to be a source of free radicals and may play important roles in the pathogenesis of cerebral ischemic injury.
最近有报道称哺乳动物大脑中存在尿酸，但尚未形成共识。人们一直认为哺乳动物大脑缺乏黄嘌呤氧化酶，而在其他组织中，黄嘌呤氧化酶催化次黄嘌呤转化为黄嘌呤以及黄嘌呤转化为尿酸，这是ATP降解的最后步骤。我们使用高效液相色谱法对大鼠脑缺血后的大脑中的次黄嘌呤、黄嘌呤和尿酸进行了测定。结果证实，在取出的大脑中，这三种物质均显著增加，且这些增加的时间顺序与代谢途径中的顺序一致。黄嘌呤氧化酶的特异性抑制剂别嘌呤醇显著抑制了尿酸和黄嘌呤的增加，并观察到次黄嘌呤的代偿性积累。从这些结果可以得出结论，尿酸确实存在于大脑中，缺血后会增加，并且可能是大脑中嘌呤降解的终产物。此外，可以推测大脑中存在黄嘌呤氧化酶，它催化从次黄嘌呤到黄嘌呤再到尿酸的反应。这些由黄嘌呤氧化酶催化的反应被认为是自由基的来源，可能在脑缺血损伤的发病机制中起重要作用。
