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尿 8-羟基-2'-脱氧鸟苷水平与阿尔茨海默病的血浆对氧磷酶 1 活性。

Urinary 8-hydroxy-2'-deoxyguanosine level and plasma paraoxonase 1 activity with Alzheimer's disease.

机构信息

Department of Medical Biochemistry, Ankara Training and Research Hospital, Ministry of Health, Ankara, Turkey.

出版信息

Clin Chem Lab Med. 2011 Nov 18;50(3):529-34. doi: 10.1515/CCLM.2011.792.

DOI:10.1515/CCLM.2011.792
PMID:22098435
Abstract

BACKGROUND

Alzheimer's disease (AD) is the most frequent cause of dementia and age is the most important risk factor for AD. Aging is associated with increased free radical production and oxidative stress plays an important role in the pathogenesis of AD. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) is a biomarker indicating oxidative DNA damage. Paraoxonase 1 (PON1) is a high-density lipoprotein (HDL)-associated antioxidant enzyme and prevents especially oxidation of low-density lipoproteins. The aim of this study is to measure urinary 8-OHdG levels and serum PON1 activity in patients with AD.

METHODS

A total of 21 elderly patients diagnosed with moderate AD (10 men and 11 women, aged 76 ± 7.8 years) were included in the study. A total of 20 healthy elderly volunteers (11 men and nine women, aged 81 ± 7.2 years) were enrolled as a control group. Levels of urinary 8-OHdG, serum PON1 activity and lipid profile were determined in patients and controls.

RESULTS

Urinary 8-OHdG levels were significantly increased, but serum PON1 activity was significantly decreased in patients compared to controls. Lipid profile did not show a difference between the groups. There was a negative correlation between 8-OHdG levels and PON1 activity only in the patient group (r=-0.536). Analytical performance characteristics of the methods used were satisfactory.

CONCLUSIONS

In this study, evidence of increased oxidative DNA damage was determined in AD patients as well as decreased serum PON1 activity. Oxidant stress and oxidative DNA damage are important pathological processes in AD. The biomarkers, urinary 8-OHdG level and serum PON1 activity can be used to determine and monitor the status of patients with AD.

摘要

背景

阿尔茨海默病(AD)是痴呆症最常见的病因,年龄是 AD 的最重要危险因素。衰老与自由基产生增加有关,氧化应激在 AD 的发病机制中起着重要作用。8-羟基-2'-脱氧鸟苷(8-OHdG)是一种表明氧化 DNA 损伤的生物标志物。对氧磷酶 1(PON1)是一种高密度脂蛋白(HDL)相关的抗氧化酶,特别可防止低密度脂蛋白的氧化。本研究的目的是测量 AD 患者的尿 8-OHdG 水平和血清 PON1 活性。

方法

共纳入 21 名被诊断为中度 AD 的老年患者(10 名男性和 11 名女性,年龄 76 ± 7.8 岁)。共纳入 20 名健康的老年志愿者(11 名男性和 9 名女性,年龄 81 ± 7.2 岁)作为对照组。在患者和对照组中测定尿 8-OHdG、血清 PON1 活性和血脂谱。

结果

与对照组相比,患者的尿 8-OHdG 水平显著升高,但血清 PON1 活性显著降低。两组之间的血脂谱没有差异。仅在患者组中,8-OHdG 水平与 PON1 活性之间存在负相关(r=-0.536)。所用方法的分析性能特征令人满意。

结论

在这项研究中,AD 患者体内存在氧化 DNA 损伤增加以及血清 PON1 活性降低的证据。氧化应激和氧化 DNA 损伤是 AD 的重要病理过程。生物标志物,尿 8-OHdG 水平和血清 PON1 活性可用于确定和监测 AD 患者的病情。

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