Uric acid as a CNS antioxidant.
Uric acid as a CNS antioxidant.
复制标题
DOI：
10.3233/jad-2010-1330
复制
发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Quinn JF
中科院分区：
文献类型：
--
作者：
Bowman GL;Shannon J;Frei B;Kaye JA;Quinn JF
氧化损伤是许多中枢神经系统 (CNS) 疾病的一致发现。尿酸 (UA) 是一种有效的亲水性抗氧化剂，可通过饮食和药物进行调节。多项证据表明血浆 UA 可能调节神经系统疾病的结果，但很少有人关注 UA 的中枢神经系统水平。我们的目的是检验以下假设：脑脊液 (CSF) UA 由血浆 UA 决定，并受血脑屏障 (BBB) 完整性的影响，并与阿尔茨海默病 (AD) 认知能力下降的速度相关。此外，由于UA和抗坏血酸可能相互充当抗氧化剂，我们还探索了它们在大脑中潜在的相互作用。 32 名轻度至中度 AD 患者（简易精神状态检查 19 ± 5）参加了一项为期一年的纵向生物标志物研究，涉及标准化临床评估。在基线时收集脑脊液和血液的 UA、抗坏血酸和白蛋白。在基线时和一年后再次收集认知测量。 CSF UA 与年龄、性别和 AD 严重程度无关。 CSF 和血浆 UA 呈正相关（r = 0.669，p = 0.001），BBB 损伤与 CSF UA 水平较高相关（p = 0.028）。血浆和脑脊液 UA 与一年内认知能力下降率均未达到显着相关性。 CSF UA 和 CSF 抗坏血酸呈正相关（r = 0.388，p = 0.001）。 CSF UA 由血浆 UA 和 BBB 完整性决定的假设得到支持，UA 和抗坏血酸在 CSF 中相关但在血浆中不相关的假设得到支持。充分有力的前瞻性研究将有助于评估 UA 在 AD 一级和二级预防中的作用。
Oxidative damage is a consistent finding in a number of central nervous system (CNS) disorders. Uric acid (UA) is a potent hydrophilic antioxidant that is modified by diet and drug. Several lines of evidence suggest that plasma UA may modulate outcomes in neurologic disease, but little attention has been paid to CNS levels of UA. Our objective was to test the hypothesis that cerebrospinal fluid (CSF) UA is determined by plasma UA, modified by blood-brain barrier (BBB) integrity and associated with rate of cognitive decline in Alzheimer’s disease (AD). Also, since UA and ascorbic acid may act as antioxidants for one another, we also explored a potential interaction between them in the brain. Thirty-two patients with mild to moderate AD (Mini-Mental Status Exam 19 ± 5) participated in a longitudinal biomarker study for one year involving standardized clinical assessments. CSF and blood were collected at baseline for UA, ascorbic acid, and albumin. Cognitive measures were collected at baseline and again one year later. CSF UA was independent of age, gender, and AD severity. CSF and plasma UA were positively correlated (r = 0.669, p = 0.001) and BBB impairment was associated with higher CSF levels of UA (p = 0.028). Neither plasma nor CSF UA reached significant association with rates of cognitive decline over 1 year. CSF UA and CSF ascorbic acid were positively correlated (r = 0.388, p = 0.001). The hypothesis that CSF UA is determined by plasma UA and BBB integrity is supported, as is the hypothesis that UA and ascorbic acid are associated in CSF but not plasma. Adequately powered prospective studies would help assess any role for UA in primary and secondary prevention of AD.