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阿尔茨海默病患者血液中巯基-二硫键和氧化-还原型谷胱甘肽状态恶化。

Deteriorated thiol-disulphide and oxidized-reduced glutathione status in blood in Alzheimer's disease.

机构信息

Department of Neurology, Faculty of Medicine, Bolu Abant Izzet Baysal University, Bolu, Turkey.

Department of Biochemistry, Faculty of Medicine, Bolu Abant Izzet Baysal University, Bolu, Turkey.

出版信息

Clin Biochem. 2024 Dec;133-134:110817. doi: 10.1016/j.clinbiochem.2024.110817. Epub 2024 Sep 11.

Abstract

BACKGROUND

Alzheimer's disease (AD) is a steadily advancing neurodegenerative condition, the occurrence and prevalence of which are on the rise in various populations. Suspected factors contributing to its development encompass the buildup of amyloid β (Aβ) plaques, the formation of neurofibrillary tangles induced by tau proteins, and heightened oxidative stress. In this study, we aimed to evaluate intra-cellular glutathione status and extracellular thiol-disulphide status in patients with AD.

METHODS

Adult patients (>60 years old) diagnosed with AD based on DSM-IV diagnostic criteria were included in the study. Patients were divided into 3 groups as mild, moderate and severe according to Mini Mental Status Examination (MMSE) and clinical findings. Extracellular thiol-disulfide and intracellular oxidized-reduced glutathione status parameters for patient and control groups were analyzed before and after reduction procedures by using reaction of thiol groups with DTNB.

RESULTS

The reduced forms of both balances (native thiol (NT) and reduced glutathione (GSH)) were significantly lower in the patient group than the control group (p = 0.031 and <0.001, respectively), while oxidized forms (disulphide (SS) and oxidized glutathione (GSSG)) and SS/NT and GSSG/GSH percent ratios were significantly higher (p < 0.05 for all). The disease duration and oxidative stress were significantly higher in the severe group of AD. There was a shift in intracellular and extracellular thiol balances towards the oxidized side, along with correlations between MMSE and these balances (rho = -0.412 for SS/NT and rho = -0.488 for GSSG/GSH), with GSSG/GSH identified as a significant predictive factor (odds ratio (95 % confidence interval): 1.352 (1.136-1.610) for the moderate group and 1.829 (1.451-2.305) for the severe group.

CONCLUSIONS

These findings suggest that blood redox balance is disrupted in AD.

摘要

背景

阿尔茨海默病(AD)是一种进行性神经退行性疾病,其在各种人群中的发生和流行呈上升趋势。导致其发展的可疑因素包括淀粉样β(Aβ)斑块的堆积、tau 蛋白诱导的神经原纤维缠结的形成以及氧化应激的加剧。在这项研究中,我们旨在评估 AD 患者的细胞内谷胱甘肽状态和细胞外巯基-二硫化物状态。

方法

本研究纳入了根据 DSM-IV 诊断标准诊断为 AD 的成年患者(>60 岁)。根据 Mini 精神状态检查(MMSE)和临床发现,将患者分为轻度、中度和重度三组。通过 DTNB 与巯基基团的反应,分析患者组和对照组在还原前后细胞外巯基-二硫化物和细胞内氧化还原谷胱甘肽状态参数。

结果

与对照组相比,患者组的两种平衡的还原形式(天然巯基(NT)和还原型谷胱甘肽(GSH))均显著降低(p=0.031 和<0.001),而氧化形式(二硫化物(SS)和氧化型谷胱甘肽(GSSG))和 SS/NT 以及 GSSG/GSH 百分比比值均显著升高(所有 p<0.05)。AD 重度组的疾病持续时间和氧化应激水平显著升高。细胞内和细胞外巯基平衡向氧化侧转移,并且 MMSE 与这些平衡之间存在相关性(SS/NT 为 rho=-0.412,GSSG/GSH 为 rho=-0.488),GSSG/GSH 被确定为一个显著的预测因子(中度组的比值比(95%置信区间):1.352(1.136-1.610),重度组的比值比(95%置信区间):1.829(1.451-2.305))。

结论

这些发现表明 AD 患者的血液氧化还原平衡被打破。

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