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富马酸二甲酯对体外少突胶质细胞的作用:多发性硬化症的影响。

Effects Mediated by Dimethyl Fumarate on In Vitro Oligodendrocytes: Implications in Multiple Sclerosis.

机构信息

Department of Biology and Biotechnologies Charles Darwin, Sapienza University of Rome, 00185 Rome, Italy.

Research Centre of Neurobiology Daniel Bovet, 00185 Rome, Italy.

出版信息

Int J Mol Sci. 2022 Mar 25;23(7):3615. doi: 10.3390/ijms23073615.

DOI:10.3390/ijms23073615
PMID:35408975
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8998768/
Abstract

BACKGROUND

Dimethyl fumarate (DMF) is a drug currently in use in oral therapy for the treatment of relapsing-remitting multiple sclerosis (RRMS) due to its immunomodulatory and neuroprotective effects. The mechanisms by which DMF exerts its therapeutic effects in MS and in particular its influence on the oligodendrocytes (OLs) survival or differentiation have not yet been fully understood.

METHODS

Characterization of Oli neu cells was performed by immunocytochemistry and RT-PCR. The effect of DMF on cell proliferation and morphology was assessed by MTT assay, trypan blue staining, RT-PCR and Western blot analysis. The antioxidant and anti-inflammatory properties of DMF were analysed by ROS detection through DCFDA staining and lipid content analysis by Oil Red O staining and TLC.

RESULTS

DMF has been observed to induce a slowdown of cell proliferation, favoring the oligodendrocyte lineage cells (OLCs) differentiation. DMF has an antioxidant effect and is able to modify the lipid content even after the LPS-mediated inflammatory stimulus in Oli neu cells.

CONCLUSIONS

The results obtained confirm that DMF has anti-inflammatory and antioxidant effects also on Oli neu cells. Interestingly, it appears to promote the OLCs differentiation towards mature and potentially myelinating cells.

摘要

背景

富马酸二甲酯(DMF)是一种目前用于口服治疗复发缓解型多发性硬化症(RRMS)的药物,由于其免疫调节和神经保护作用。DMF 在多发性硬化症中发挥治疗作用的机制,特别是其对少突胶质细胞(OLs)存活或分化的影响,尚未完全了解。

方法

通过免疫细胞化学和 RT-PCR 对 Oli neu 细胞进行鉴定。通过 MTT 测定、台盼蓝染色、RT-PCR 和 Western blot 分析评估 DMF 对细胞增殖和形态的影响。通过 DCFDA 染色检测 ROS 以及油红 O 染色和 TLC 分析脂质含量来分析 DMF 的抗氧化和抗炎特性。

结果

观察到 DMF 可减缓细胞增殖,有利于少突胶质细胞系细胞(OLCs)分化。DMF 具有抗氧化作用,并且即使在 LPS 介导的 Oli neu 细胞炎症刺激后,也能够改变脂质含量。

结论

获得的结果证实,DMF 对 Oli neu 细胞也具有抗炎和抗氧化作用。有趣的是,它似乎促进了 OLCs 向成熟和潜在髓鞘形成细胞的分化。

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