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阻塞性睡眠呼吸暂停患者氧化应激诱导的循环白细胞端粒长度缩短

Oxidative Stress-induced Telomere Length Shortening of Circulating Leukocyte in Patients with Obstructive Sleep Apnea.

作者信息

Kim Kyung Soo, Kwak Jin Wook, Lim Su Jin, Park Yong Kyun, Yang Hoon Shik, Kim Hyun Jik

机构信息

2Department of Otorhinolaryngology and Head & Neck Surgery, Chung-Ang University College of Medicine, Seoul, Korea.

1Department of Otorhinolaryngology, Seoul National University College of Medicine.

出版信息

Aging Dis. 2016 Oct 1;7(5):604-613. doi: 10.14336/AD.2016.0215. eCollection 2016 Oct.

Abstract

The main mechanism of pathogenesis which causes systemic complications in obstructive sleep apnea (OSA) patients is believed to be intermittent hypoxia-induced intermediary effect and it depends on the burden of oxidative stress during sleep. We aimed to search the predictive markers which reflect the burden of systemic oxidative stress in patients with OSA and whether excessive telomere length shortening is a characteristic feature that can assess oxidative stress levels. We used quantitative PCR to measure telomere length using peripheral blood genomic DNA. Telomere lengths were compared in an age- and body mass index (BMI)-dependent manner in 34 healthy volunteers and 43 OSA subjects. We also performed reactive oxygen species assay to measure the concentration of hydrogen peroxide in the peripheral blood of healthy volunteers and OSA subjects. We found that the serum concentration of hydrogen peroxide was considerably higher in OSA patients, and that this was closely related with the severity of OSA. Significantly shortened telomere length was observed in the circulating leukocytes of the peripheral blood of OSA patients, and telomere length shortening was aggravated more acutely in an age- and BMI-dependent manner. An inverse correlation was observed between the concentration of hydrogen peroxide and the telomere length of OSA patients and excessive telomere length shortening was also linked to severity of OSA. The results provided evidence that telomere length shortening or excessive cellular aging might be distinctive in circulating leukocyte of OSA patients and may be an predictive biomarker for reflect the burden of oxidative stress in the peripheral blood of OSA patients.

摘要

阻塞性睡眠呼吸暂停(OSA)患者发生全身并发症的主要发病机制被认为是间歇性缺氧诱导的中介效应,且这取决于睡眠期间氧化应激的负担。我们旨在寻找反映OSA患者全身氧化应激负担的预测标志物,以及端粒长度过度缩短是否是一种可评估氧化应激水平的特征性表现。我们使用定量聚合酶链反应(PCR),通过外周血基因组DNA来测量端粒长度。在34名健康志愿者和43名OSA受试者中,以年龄和体重指数(BMI)相关的方式比较端粒长度。我们还进行了活性氧检测,以测量健康志愿者和OSA受试者外周血中过氧化氢的浓度。我们发现,OSA患者血清中过氧化氢的浓度明显更高,且这与OSA的严重程度密切相关。在OSA患者外周血的循环白细胞中观察到端粒长度显著缩短,并且端粒长度缩短在年龄和BMI相关的方式下更急剧地加重。在OSA患者中,观察到过氧化氢浓度与端粒长度呈负相关,并且端粒长度过度缩短也与OSA的严重程度有关。结果提供了证据,表明端粒长度缩短或细胞过度老化在OSA患者的循环白细胞中可能是独特的,并且可能是反映OSA患者外周血氧化应激负担的预测生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a627/5036955/3fc9bc29075c/ad-7-5-604-g1.jpg

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