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过氧化物酶体是多发性硬化症和视神经脊髓炎谱系疾病发病机制中的关键因素。

Peroxiredoxins are involved in the pathogenesis of multiple sclerosis and neuromyelitis optica spectrum disorder.

机构信息

Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan.

出版信息

Clin Exp Immunol. 2020 Nov;202(2):239-248. doi: 10.1111/cei.13487. Epub 2020 Jul 23.

Abstract

Peroxiredoxins (PRXs) are intracellular anti-oxidative enzymes but work as inflammatory amplifiers under the extracellular condition. To date, the function of PRXs in the pathogenesis of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) is not fully understood. The aim of this study was to investigate whether PRXs play a role in the pathogenesis of MS and NMOSD. We analyzed levels of PRXs (PRX1, PRX5 and PRX6) in the cerebrospinal fluid (CSF) and serum of 16 patients with MS, 16 patients with NMOSD and 15 patients with other neurological disorders (ONDs). We identified potential correlations between significantly elevated PRXs levels and the clinical variables in patients with MS and NMOSD. Additionally, pathological analyses of PRXs (PRX1-6) in the central nervous system (CNS) were performed using the experimental autoimmune encephalomyelitis (EAE), animal model of MS. We found that serum levels of PRX5 and PRX6 in patients with MS and NMOSD were higher compared with those in patients with ONDs (P < 0·05). Furthermore, high levels of PRX5 and PRX6 were partly associated with blood-brain barrier dysfunction and disease duration in NMOSD patients. No significant elevation was found in CSF PRXs levels of MS and NMOSD. Spinal cords from EAE mice showed remarkable PRX5 staining, especially in CD45 infiltrating cells. In conclusion, PRX5 and PRX6 may play a role in the pathogeneses of MS and NMOSD.

摘要

过氧化物酶(PRXs)是细胞内抗氧化酶,但在细胞外条件下可作为炎症放大器。迄今为止,PRXs 在多发性硬化症(MS)和视神经脊髓炎谱系障碍(NMOSD)发病机制中的作用尚未完全阐明。本研究旨在探讨 PRXs 是否在 MS 和 NMOSD 的发病机制中发挥作用。我们分析了 16 例 MS 患者、16 例 NMOSD 患者和 15 例其他神经疾病(ONDs)患者的脑脊液(CSF)和血清中 PRXs(PRX1、PRX5 和 PRX6)水平。我们确定了 MS 和 NMOSD 患者中 PRXs 水平显著升高与临床变量之间的潜在相关性。此外,使用实验性自身免疫性脑脊髓炎(EAE),MS 的动物模型,对中枢神经系统(CNS)中 PRXs(PRX1-6)进行了病理分析。我们发现 MS 和 NMOSD 患者的血清 PRX5 和 PRX6 水平高于 ONDs 患者(P<0·05)。此外,PRX5 和 PRX6 的高水平部分与 NMOSD 患者的血脑屏障功能障碍和疾病持续时间有关。MS 和 NMOSD 的 CSF PRXs 水平无明显升高。EAE 小鼠的脊髓显示出明显的 PRX5 染色,特别是在 CD45 浸润细胞中。总之,PRX5 和 PRX6 可能在 MS 和 NMOSD 的发病机制中发挥作用。

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