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不同程度 NOX2 调节的受试者血小板与尿 8-异前列腺素 F2α 水平的关系。

Relationship between platelet and urinary 8-Iso-PGF2α levels in subjects with different degrees of NOX2 regulation.

机构信息

Clinica Medica, University of Rome "La Sapienza", Rome, Italy.

出版信息

J Am Heart Assoc. 2013 Jun 14;2(3):e000198. doi: 10.1161/JAHA.113.000198.

DOI:10.1161/JAHA.113.000198
PMID:23770972
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3698784/
Abstract

BACKGROUND

Urinary 8-iso-PGF2α, a marker of oxidative stress, is influenced by the activation of NOX2. It is unclear if platelets 8-iso-PGF2α contribute to urinary 8-iso-PGF2α.

METHODS AND RESULTS

In a cross-sectional study, platelet, urinary, and serum 8-iso-PGF2α were determined in subjects with downregulation (X-linked chronic granulomatous disease [X-CGD], n=25) and upregulation (type II diabetic patients [T2D], n=121) of NOX2 and 153 controls matched for sex and age. In diabetic patients (n=18), the above variables were repeated before and after 7 days treatment with 100 mg/day aspirin or 100 mg/day aspirin plus 40 mg/day atorvastatin. In vitro study was performed to see the contribution of blood cells to serum 8-iso-PGF2α. Compared with controls, X-CGD patients had lower platelet, serum, and urinary 8-iso-PGF2α values; conversely, diabetic patients had higher values of 8-iso-PGF2α compared with controls. Urinary 8-iso-PGF2α significantly correlated with both platelet and serum 8-iso-PGF2α in the 2 cohorts. A parallel increase of platelet, serum, and urinary 8-iso-PGF2α by aspirin and a parallel decrease by aspirin plus atorvastatin were detected in the interventional study. In vitro study demonstrated that platelets contribute to 37% of serum 8-iso-PGF2α and that only 13% of it is of extravascular origin.

CONCLUSIONS

The study suggests that NOX2 contributes to the formation of 8-iso-PGF2α in both platelets and urine. The direct correlation between platelet and urinary 8-iso-PGF2α suggests that, at least partly, urinary 8-iso-PGF2α reflects platelet 8-iso-PGF2α production. Analysis of serum 8-iso-PGF2α may represent a novel tool to investigate the production of 8-iso-PGF2α by blood cells including platelets.

CLINICAL TRIAL REGISTRATION

URL: ClinicalTrials.gov. Unique Identifier: NCT01250340.

摘要

背景

尿液 8-异前列腺素 F2α(8-iso-PGF2α)是氧化应激的标志物,其水平受 NOX2 激活的影响。目前尚不清楚血小板 8-iso-PGF2α 是否会导致尿液 8-iso-PGF2α 升高。

方法和结果

在一项横断面研究中,检测了下调(X 连锁慢性肉芽肿病[X-CGD],n=25)和上调(2 型糖尿病患者[T2D],n=121)NOX2 以及 153 名性别和年龄匹配的对照组的血小板、尿液和血清 8-iso-PGF2α。在 18 例糖尿病患者中,在服用 100 mg/天阿司匹林或 100 mg/天阿司匹林加 40 mg/天阿托伐他汀治疗前和治疗后 7 天重复了上述变量。进行了体外研究以观察血细胞对血清 8-iso-PGF2α 的贡献。与对照组相比,X-CGD 患者的血小板、血清和尿液 8-iso-PGF2α 水平较低;相反,糖尿病患者的 8-iso-PGF2α 水平高于对照组。在这两个队列中,尿液 8-iso-PGF2α 与血小板和血清 8-iso-PGF2α 均呈显著相关。在干预研究中,我们发现阿司匹林可使血小板、血清和尿液 8-iso-PGF2α 呈平行增加,而阿司匹林加阿托伐他汀可使 8-iso-PGF2α 呈平行降低。体外研究表明,血小板占血清 8-iso-PGF2α 的 37%,而仅有 13%来自血管外。

结论

该研究表明,NOX2 参与了血小板和尿液中 8-iso-PGF2α 的形成。血小板和尿液 8-iso-PGF2α 之间的直接相关性表明,至少部分情况下,尿液 8-iso-PGF2α 反映了血小板 8-iso-PGF2α 的产生。分析血清 8-iso-PGF2α 可能代表一种新的工具,用于研究包括血小板在内的血细胞产生 8-iso-PGF2α。

临床试验注册

网址:ClinicalTrials.gov。唯一标识符:NCT01250340。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/137d/3698784/b6e6cd06e0c8/jah3-2-e000198-g5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/137d/3698784/5b55195a8fbb/jah3-2-e000198-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/137d/3698784/84c4e00c4b2d/jah3-2-e000198-g2.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/137d/3698784/63252ba65432/jah3-2-e000198-g4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/137d/3698784/b6e6cd06e0c8/jah3-2-e000198-g5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/137d/3698784/5b55195a8fbb/jah3-2-e000198-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/137d/3698784/84c4e00c4b2d/jah3-2-e000198-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/137d/3698784/e6755ecd9fc4/jah3-2-e000198-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/137d/3698784/63252ba65432/jah3-2-e000198-g4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/137d/3698784/b6e6cd06e0c8/jah3-2-e000198-g5.jpg

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