Oxidative stress leads to reduction of plasmalogen serving as a novel biomarker for systemic lupus erythematosus
Oxidative stress leads to reduction of plasmalogen serving as a novel biomarker for systemic lupus erythematosus
复制标题
氧化应激导致缩醛磷脂减少，缩醛磷脂是系统性红斑狼疮的新型生物标志物
DOI：
10.1016/j.freeradbiomed.2016.11.006
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发表时间：
2016-12-01
影响因子：
7.4
通讯作者：
Wen, Chengping
中科院分区：
文献类型：
--
作者：
Hu, Changfeng;Zhou, Jia;Wen, Chengping
系统性红斑狼疮（SLE）患者体内氧化应激水平升高，并与SLE发病机制密切相关。然而，由于氧化应激的不稳定性、非特异性和不能代表所有SLE症状，目前还没有常用的氧化应激指标用于常规临床。此外，用于活性氧物种的可重复分析的方法仍然缺乏。脂质及其代谢产物是生物系统的重要组成部分，其中许多是氧化应激的分子靶点，在信号传导、炎症和免疫反应中起着至关重要的作用。因此，确定脂质及其代谢产物的变化水平可能会服务于SLE研究的需要。在初步研究中，对来自30名SLE患者和30名对照的血清进行了鸟枪脂质组学分析，结果显示对照和患者血清中乙醇胺缩醛磷脂（pPE）种类分别从85.03 +/- 3.06 nmol/mL显著减少至62.39 +/- 4.34 nmol/mL，伴随患者中lysoPE（LPE）含量（类似于46摩尔%）和4-羟基壬烯醛（氧化应激的指标）的显著增加。还测定了代表性的促炎细胞因子，揭示了SLE患者中IL-6、IL-10和TNF-α的显著升高。多变量和多元回归分析首次显示SLE疾病活动指数、IL-10水平和pPE含量之间存在显著相关性，为SLE发病机制提供了见解。本研究还表明，pPE（氧化应激的分子靶点）及其过氧化产物的变化可能成为诊断SLE的新的生物标志物。
Oxidative stress is elevated in systemic lupus erythematosus (SLE) patients, and associated extensively with SLE pathogenesis. However, no common indicators of oxidative stress are yet in routine clinical use because of their instability, nonspecificity, and non-representation of all SLE symptoms. Moreover, the method for reproducible analysis of reactive oxygen species is still lacking. Lipids and their metabolites are essential components of biological systems, many of which serve as molecular targets of oxidative stress and play crucial roles in signaling, inflammation, and immune responses. Thus, determining the changed levels of lipids and their metabolites may serve the needs for SLE research. In the pilot study, shotgun lipidomics of sera from 30 SLE patients and 30 controls was performed and revealed a marked reduction of ethanolamine plasmalogen (pPE) species from 85.03 +/- 3.06 to 62.39 +/- 4.34 nmol/mL serum in controls and patients, respectively, accompanying significant increases in lysoPE (LPE) content (similar to 46 mol%) and 4-hydroxynonenal (an indictor of oxidative stress) in patients. Representative proinflammatory cytokines were also determined, revealing significant elevation of IL-6, IL-10, and TNF-alpha in SLE patients. Multivariate and multiple regression analyses showed for the first time that significant correlation among the SLE disease activity index, IL-10 levels, and pPE content exists, providing insights into SLE pathogenesis. The study also indicates that the changes of pPE (molecular targets of oxidative stress) and their peroxidation products may serve as novel biomarkers for diagnosis of SLE.