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轻度认知障碍和阿尔茨海默病的外周氧化应激生物标志物。

Peripheral oxidative stress biomarkers in mild cognitive impairment and Alzheimer's disease.

机构信息

Department of Clinical Chemistry and Toxicology, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.

出版信息

J Alzheimers Dis. 2011;26(1):59-68. doi: 10.3233/JAD-2011-110284.

Abstract

Oxidative stress has been associated with normal aging and Alzheimer's disease (AD). However, little is known about oxidative stress in mild cognitive impairment (MCI) patients who present a high risk for developing AD. The aim of this study was to investigate plasma production of the lipid peroxidation marker, malonaldehyde (MDA) and to determine, in erythrocytes, the enzymatic antioxidant activity of catalase, glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione S-transferase (GST) in 33 individuals with MCI, 29 with mild probable AD and 26 healthy aged subjects. GR/GPx activity ratio was calculated to better assess antioxidant defenses. The relationship between oxidative stress and cognitive performance was also evaluated by the Mini Mental State Examination (MMSE). AD patients showed higher MDA levels than both MCI and healthy elderly subjects. MCI subjects also exhibited higher MDA levels compared to controls. Catalase and GPx activity were similar in MCI and healthy individuals but higher in AD. GR activity was lower in MCI and AD patients than in healthy aged subjects. Additionally, GR/GPx ratio was higher in healthy aged subjects, intermediate in MCI and lower in AD patients. No differences in GST activity were detected among the groups. MMSE was negatively associated with MDA levels (r = -0.31, p = 0.028) and positively correlated with GR/GPx ratio in AD patients (r = 0.68, p < 0.001). MDA levels were also negatively correlated to GR/GPx ratio (r = -0.31, p = 0.029) in the AD group. These results suggest that high lipid peroxidation and decreased antioxidant defenses may be present early in cognitive disorders.

摘要

氧化应激与正常衰老和阿尔茨海默病(AD)有关。然而,对于轻度认知障碍(MCI)患者,他们有很高的发展为 AD 的风险,但对于他们的氧化应激知之甚少。本研究旨在研究血浆丙二醛(MDA)的脂质过氧化标记物的产生,并确定红细胞中过氧化氢酶、谷胱甘肽过氧化物酶(GPx)、谷胱甘肽还原酶(GR)和谷胱甘肽 S-转移酶(GST)的酶抗氧化活性。研究对象包括 33 名 MCI 患者、29 名轻度可能 AD 患者和 26 名健康老年受试者。为了更好地评估抗氧化防御能力,还计算了 GR/GPx 活性比。通过简易精神状态检查(MMSE)评估氧化应激与认知表现之间的关系。AD 患者的 MDA 水平高于 MCI 和健康老年人。MCI 患者的 MDA 水平也高于对照组。CAT 和 GPx 活性在 MCI 和健康个体中相似,但在 AD 中较高。GR 活性在 MCI 和 AD 患者中低于健康老年人。此外,GR/GPx 比值在健康老年人中较高,在 MCI 中中等,在 AD 患者中较低。各组 GST 活性无差异。MMSE 与 MDA 水平呈负相关(r = -0.31,p = 0.028),与 AD 患者的 GR/GPx 比值呈正相关(r = 0.68,p <0.001)。MDA 水平与 AD 组的 GR/GPx 比值也呈负相关(r = -0.31,p = 0.029)。这些结果表明,在认知障碍早期可能存在高脂质过氧化和抗氧化防御能力降低。

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