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肺动脉高压患者中氧化应激与一氧化氮信号相关生物标志物:一项病例对照研究

Oxidative stress and nitric oxide signaling related biomarkers in patients with pulmonary hypertension: a case control study.

作者信息

Zhang Shuai, Yang Ting, Xu Xiaomao, Wang Meng, Zhong Linye, Yang Yuanhua, Zhai Zhenguo, Xiao Fei, Wang Chen

机构信息

Department of Pulmonary and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People's Republic of China.

Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Beijing, People's Republic of China.

出版信息

BMC Pulm Med. 2015 May 2;15:50. doi: 10.1186/s12890-015-0045-8.

DOI:10.1186/s12890-015-0045-8
PMID:25934483
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4477508/
Abstract

BACKGROUND

Oxidative stress (OS) and reduced nitric oxide (NO) bioavailability contribute to the pathogenesis of pulmonary hypertension (PH). Whether there are associations between OS and NO signaling biomarkers and whether these biomarkers are associated with the severity of PH remain unclear.

METHODS

Blood samples were collected from 35 healthy controls and 35 patients with pulmonary arterial hypertension (PAH, n = 12) or chronic thromboembolic pulmonary hypertension (CTEPH, n = 23). The mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance index (PVRI) were measured by right heart catheterization. We measured the derivative of reactive oxygen molecules (d-ROMs), biological antioxidant potential (BAP) and superoxide dismutase (SOD) by automatic biochemical analyzer, malondialdehyde (MDA) and asymmetric dimethylarginine (ADMA) by enzyme-linked immunosorbent assay. The relationship between oxidative-antioxidative biomarkers and ADMA, as well as their association with pulmonary hemodynamics, were analyzed.

RESULTS

Compared with age- and gender-matched controls, there was no significant difference of d-ROMs in PAH and CTEPH patients; MDA was increased in CTEPH patients (P = 0.034); BAP and SOD were decreased in PAH (P = 0.014, P < 0.001) and CTEPH patients (P = 0.015, P < 0.001); ADMA level was significantly higher in PAH (P = 0.007) and CTEPH patients (P < 0.001). No association between oxidative-antioxidative biomarkers and ADMA was found. Serum ADMA concentration was correlated with mPAP (r = 0.762, P = 0.006) and PVRI (r = 0.603, P = 0.038) in PAH patients.

CONCLUSIONS

The antioxidative potential and NO signaling are impaired in PAH and CTEPH. Increased serum ADMA level is associated with unfavorable pulmonary hemodynamics in PAH patients. Thus, ADMA may be useful in the severity evaluation and risk stratification of PAH.

摘要

背景

氧化应激(OS)和一氧化氮(NO)生物利用度降低参与了肺动脉高压(PH)的发病机制。OS与NO信号生物标志物之间是否存在关联,以及这些生物标志物是否与PH的严重程度相关尚不清楚。

方法

采集35名健康对照者以及35例肺动脉高压(PAH,n = 12)或慢性血栓栓塞性肺动脉高压(CTEPH,n = 23)患者的血样。通过右心导管插入术测量平均肺动脉压(mPAP)和肺血管阻力指数(PVRI)。使用自动生化分析仪测量活性氧分子衍生物(d-ROMs)、生物抗氧化能力(BAP)和超氧化物歧化酶(SOD),采用酶联免疫吸附测定法测量丙二醛(MDA)和不对称二甲基精氨酸(ADMA)。分析氧化-抗氧化生物标志物与ADMA之间的关系,以及它们与肺血流动力学的关联。

结果

与年龄和性别匹配的对照组相比,PAH和CTEPH患者的d-ROMs无显著差异;CTEPH患者的MDA升高(P = 0.034);PAH(P = 0.014,P < 0.001)和CTEPH患者(P = 0.015,P < 0.001)的BAP和SOD降低;PAH(P = 0.007)和CTEPH患者(P < 0.001)的ADMA水平显著升高。未发现氧化-抗氧化生物标志物与ADMA之间存在关联。PAH患者血清ADMA浓度与mPAP(r = 0.762,P = 0.006)和PVRI(r = 0.603,P = 0.038)相关。

结论

PAH和CTEPH患者的抗氧化能力和NO信号受损。PAH患者血清ADMA水平升高与不良的肺血流动力学相关。因此,ADMA可能有助于PAH的严重程度评估和风险分层。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94e5/4477508/d581433a0715/12890_2015_45_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94e5/4477508/f3a29e4c4ac4/12890_2015_45_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94e5/4477508/d581433a0715/12890_2015_45_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94e5/4477508/f3a29e4c4ac4/12890_2015_45_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94e5/4477508/d581433a0715/12890_2015_45_Fig2_HTML.jpg

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