Uric acid administration in patients with acute stroke: a novel approach to neuroprotection.
Uric acid administration in patients with acute stroke: a novel approach to neuroprotection.
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DOI：
10.1586/14737175.8.2.259
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发表时间：
2008-02-01
影响因子：
4.3
通讯作者：
Chamorro, Angel
中科院分区：
文献类型：
--
作者：
Amaro, Sergio;Planas, Anna M;Chamorro, Angel
尿酸（UA）是人体嘌呤分解代谢的最终产物，是一种强大的抗氧化剂，在缺血条件下其生成量会增加。然而，临床和实验研究都表明，短暂性脑缺血后抗氧化能力会逐渐耗尽，这种消耗的程度似乎与脑组织损伤的程度、梗死的进展、急性期神经功能损伤的严重程度以及长期功能结果相关。越来越多的证据支持脑缺血后给予 UA 的神经保护作用。在实验条件下，UA 在脑缺血机械模型（大脑中动脉短暂或永久性管腔内闭塞）和自体凝块注射的血栓栓塞模型中均具有神经保护作用。 UA 对健康志愿者的管理是可行且安全的。在接受重组组织纤溶酶原激活剂 (rt-PA) 治疗的急性中风患者中，联合使用 UA 已被证明可以减少脂质过氧化，并防止中风发作后早期发生的 UA 血液水平下降。目前，一项多中心 III 期临床试验正在测试 UA 的给药是否可以增加 rt-PA 的临床益处，rt-PA 是急性缺血性中风患者唯一获批的治疗方法。这篇综述总结了现有的信息，证明这种新颖的治疗方法在这种毁灭性的临床病症中是合理的。
Uric acid (UA) is the end product of purine catabolism in humans and is a powerful antioxidant whose generation is increased under ischemic conditions. However, both clinical and experimental studies reveal a gradual exhaustion of the antioxidant capacity after transient cerebral ischemia, and the magnitude of this consumption seems to be correlated with the extent of brain tissue injury, growth of the infarction, severity of neurological impairment in the acute phase, and long-term functional outcome. Growing evidence supports the neuroprotective effect of UA administration after brain ischemia. In experimental conditions, the administration of UA is neuroprotective both in mechanical models of brain ischemia (transient or permanent intraluminal occlusion of the middle cerebral artery) and in thromboembolic models of autologous clot injection. The administration of UA is feasible and safe in healthy volunteers. In acute stroke patients treated with recombinant tissue plasminogen activator (rt-PA), co-administration of UA has proven to reduce lipid peroxidation and to prevent the fall in UA blood levels that occur very early after stroke onset. Currently, a multicentric Phase III clinical trial is testing whether the administration of UA increases the clinical benefits of rt-PA, which represents the only approved therapy in patients with acute ischemic stroke. This review summarizes the available information justifying such a novel therapeutic approach in this devastating clinical condition.