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早期多发性硬化症患者的脂蛋白谱:慢性炎症的影响?

Lipoprotein profiling in early multiple sclerosis patients: effect of chronic inflammation?

机构信息

Institute of Clinical and Translational Research, Biomedical Research Center, Slovak Academy of Sciences, Dúbravská cesta 9, SK 845 05, Bratislava, Slovakia.

1st Department of Neurology, Faculty of Medicine, Comenius University, Bratislava, Slovakia.

出版信息

Lipids Health Dis. 2020 Mar 17;19(1):49. doi: 10.1186/s12944-020-01221-x.

Abstract

BACKGROUND

Inflammatory cytokines contribute to proatherogenic changes in lipid metabolism by reduction of HDL-cholesterol (HDL-C) levels, impairment of its antiinflammatory and antioxidant functions. Therefore, the protective actions of HDL-C can be limited in chronic inflammatory diseases such as multiple sclerosis (MS). The aim of this study was to assess the association between lipoprotein subfractions and inflammatory status in early stages of multiple sclerosis.

METHODS

Polyacrylamide gel electrophoresis Lipoprint© System was used for lipoprotein profile analysis in 19 newly diagnosed MS patients, and in matched 19 healthy controls. Serum levels of interleukin (IL) 1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p70), IL-13, IL-17, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor, interferon-γ and TNF-α were measured by multiplex bead assay.

RESULTS

Concentrations of the measured cytokines and lipoprotein subclasses were comparable between MS patients and controls. Male, but not female MS patients had significantly higher total HDL-C and small HDL-C subfraction than healthy controls. Large HDL-C negatively correlated with all measured cytokines except IL-17 in MS but not in controls. Intermediate HDL-C subfractions correlated positively with all measured cytokines except G-CSF in MS females but not in MS males or controls.

CONCLUSION

Our results of higher HDL-C and mainly its small HDL-C subfraction suggest that male MS patients are at higher risk of atherosclerosis and the subtle dyslipidemia is present in early stages of the disease. The correlations between specific HDL-C subfractions and the inflammatory cytokines demonstrate mutual links between systemic inflammation and lipid metabolism in MS.

TRIAL REGISTRATION

ClinicalTrials.gov, Identifier: NCT03052595 Registered on Feb 14, 2017.

摘要

背景

炎症细胞因子通过降低高密度脂蛋白胆固醇(HDL-C)水平,损害其抗炎和抗氧化功能,导致脂质代谢发生动脉粥样硬化前变化。因此,HDL-C 的保护作用在多发性硬化症(MS)等慢性炎症性疾病中可能受到限制。本研究旨在评估脂蛋白亚组分与多发性硬化症早期炎症状态之间的关系。

方法

使用聚丙酰胺凝胶电泳 Lipoprint©系统对 19 例新诊断的 MS 患者和 19 例匹配的健康对照者的脂蛋白谱进行分析。采用多因子珠粒分析测定血清白细胞介素(IL)1β、IL-2、IL-4、IL-5、IL-6、IL-7、IL-8、IL-10、IL-12(p70)、IL-13、IL-17、粒细胞集落刺激因子(G-CSF)、粒细胞-巨噬细胞集落刺激因子、干扰素-γ和 TNF-α的水平。

结果

MS 患者和对照组之间测量的细胞因子和脂蛋白亚组分的浓度无差异。与健康对照组相比,男性 MS 患者的总 HDL-C 和小 HDL-C 亚组分显著升高,但女性患者无差异。在 MS 患者中,大 HDL-C 与除 IL-17 以外的所有测量细胞因子呈负相关,但在对照组中无相关性。在 MS 女性患者中,中间 HDL-C 亚组分与除 G-CSF 以外的所有测量细胞因子呈正相关,但在 MS 男性或对照组中无相关性。

结论

我们的研究结果表明,男性 MS 患者的 HDL-C 水平升高,主要是小 HDL-C 亚组分升高,这表明他们患动脉粥样硬化的风险更高,而且在疾病的早期就存在血脂代谢异常。特定 HDL-C 亚组分与炎症细胞因子之间的相关性表明,系统性炎症与 MS 患者的脂质代谢之间存在相互联系。

试验注册

ClinicalTrials.gov,标识符:NCT03052595,于 2017 年 2 月 14 日注册。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d12/7076999/e068febc4192/12944_2020_1221_Fig1_HTML.jpg

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