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慢性阻塞性肺疾病中活性过硫酸盐物质的产生。

Production of reactive persulfide species in chronic obstructive pulmonary disease.

机构信息

Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.

Department of Environmental Health Sciences and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai, Japan.

出版信息

Thorax. 2017 Dec;72(12):1074-1083. doi: 10.1136/thoraxjnl-2016-209359. Epub 2017 Jul 19.

Abstract

BACKGROUND

Oxidative stress is a major aetiological factor driving chronic obstructive pulmonary disease (COPD). Recently recognised as potent antioxidants, reactive persulfide and polysulfide species are biosynthesised by cystathionine β-synthase and cystathionine γ-lyase. The production of reactive persulfide and polysulfide species in the lungs of patients with COPD remain unknown.

OBJECTIVES

The aim of this study was to examine the production of reactive persulfides and polysulfides, such as glutathione persulfide (GSSH), cysteine persulfide (CysSSH) and glutathione trisulfide (GSSSH), in lung-resident cells and epithelial lining fluid (ELF) obtained from patients with mild to moderate COPD.

METHODS

Lung tissues, primary lung cells, ELF and sputum were obtained. The amounts of reactive persulfides and polysulfides in the cells and ELF were measured by liquid chromatography-tandem mass spectrometry with β-(4-hydroxyphenyl) ethyl iodoacetamide as a trapping agent for hydroper/polysulfides. The amounts of synthases in the lung tissues, sputum and primary cells were quantified.

RESULTS

The amounts of GSSH, CysSSH and GSSSH were decreased in the lung cells and ELF from patients with COPD. The amounts of reactive persulfides and polysulfides in the lung cells had a positive correlation with the degree of airflow limitation. By contrast, the amounts of the synthases were increased in the lung tissues and sputum cells of patients with COPD.

CONCLUSIONS

We have identified a decrease in reactive persulfide and polysulfide species in the lungs of patients with COPD. These data suggest that the newly detected antioxidants reactive persulfides and polysulfides could be associated with the redox balance in the lungs of patients with COPD.

摘要

背景

氧化应激是导致慢性阻塞性肺疾病(COPD)的主要病因。最近被认为是有效的抗氧化剂,活性过硫化物和多硫化物是由半胱氨酸β-合酶和半胱氨酸γ-裂合酶生物合成的。COPD 患者肺部活性过硫化物和多硫化物的产生尚不清楚。

目的

本研究旨在检测肺驻留细胞和上皮衬液(ELF)中活性过硫化物和多硫化物(如谷胱甘肽过硫化物(GSSH)、半胱氨酸过硫化物(CysSSH)和谷胱甘肽三硫化物(GSSSH))在轻度至中度 COPD 患者中的产生情况。

方法

获取肺组织、原代肺细胞、ELF 和痰液。用液相色谱-串联质谱法,用β-(4-羟苯基)乙基碘乙酰胺作为过硫化物/多硫化物的捕获剂,测量细胞和 ELF 中活性过硫化物和多硫化物的含量。定量肺组织、痰液和原代细胞中的合酶含量。

结果

COPD 患者的肺细胞和 ELF 中 GSSH、CysSSH 和 GSSSH 的含量降低。肺细胞中活性过硫化物和多硫化物的含量与气流受限程度呈正相关。相比之下,COPD 患者的肺组织和痰液细胞中的合酶含量增加。

结论

我们已经确定 COPD 患者肺部的活性过硫化物和多硫化物含量减少。这些数据表明,新发现的抗氧化剂活性过硫化物和多硫化物可能与 COPD 患者肺部的氧化还原平衡有关。

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