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同型半胱氨酸可能有助于阿尔茨海默病大脑中 RNA 损伤的发病机制。

Homocysteine may contribute to pathogenesis of RNA damage in brains with Alzheimer's disease.

机构信息

Department of Neurology, Chitose Daiichi Hospital, Chitose, Hokkaido 066-0042, Japan.

出版信息

Neurodegener Dis. 2009;6(5-6):252-7. doi: 10.1159/000262443. Epub 2009 Nov 26.

Abstract

BACKGROUND

The pathogenesis of Alzheimer's disease (AD) is related to homocysteine (HC), but the details are unknown.

OBJECTIVE

We aimed to measure the cerebrospinal fluid (CSF) concentrations of 8-hydroxyguanosine (8-OHG), considering RNA oxidative damage marker, free HC and total HC in the CSF of patients with AD and in normal control subjects.

METHOD AND PATIENTS

Subjects were 18 untreated patients with AD (M/F = 7/11) and 15 age-matched controls (M/F = 9/6), with a mean age +/- SD of 67.4 +/- 5.0 years for patients and of 65.7 +/- 9.2 years for controls. The concentrations of free HC, total HC and 8-OHG in the CSF of AD patients were measured by high-performance liquid chromatography using an electrochemical detector. The control subjects were neurologically normal patients who underwent lumbar spinal anesthesia for minor surgery.

RESULTS

Total HC and 8-OHG concentrations were significantly increased, and there was a significant positive correlation between total HC and 8-OHG concentrations. However, the concentration of 8-OHG in the CSF showed no correlation with 8-OHG in serum and was not significantly altered in AD patients.

CONCLUSION

These results suggest that total HC and 8-OHG are positively correlated and may be related to AD pathogenesis due to RNA-associated oxidative damage linked to total HC.

摘要

背景

阿尔茨海默病(AD)的发病机制与同型半胱氨酸(HC)有关,但具体细节尚不清楚。

目的

我们旨在测量 AD 患者和正常对照组患者脑脊液(CSF)中的 8-羟基鸟嘌呤(8-OHG)浓度,同时考虑 RNA 氧化损伤标志物、CSF 中的游离 HC 和总 HC。

方法和患者

受试者为 18 名未经治疗的 AD 患者(M/F = 7/11)和 15 名年龄匹配的对照组(M/F = 9/6),患者的平均年龄 +/- SD 为 67.4 +/- 5.0 岁,对照组为 65.7 +/- 9.2 岁。AD 患者的 CSF 中游离 HC、总 HC 和 8-OHG 浓度通过高效液相色谱法和电化学检测器进行测量。对照组为接受腰椎麻醉进行小手术的神经正常患者。

结果

总 HC 和 8-OHG 浓度显著升高,总 HC 和 8-OHG 浓度之间存在显著正相关。然而,CSF 中 8-OHG 的浓度与血清中 8-OHG 无相关性,且 AD 患者中未发生显著改变。

结论

这些结果表明,总 HC 和 8-OHG 呈正相关,可能与 RNA 相关氧化损伤与总 HC 有关,从而与 AD 的发病机制有关。

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