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阿帕米胺给药对铜锌诱导的多发性硬化症模型中 miR-219 和 miR-155-3p 表达的影响。

Apamin administration impact on miR-219 and miR-155-3p expression in cuprizone induced multiple sclerosis model.

机构信息

School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences and Health Services, Isfahan, Iran.

Department of Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences and Health Services, Isfahan, Iran.

出版信息

Mol Biol Rep. 2020 Nov;47(11):9013-9019. doi: 10.1007/s11033-020-05959-6. Epub 2020 Nov 10.

Abstract

Multiple sclerosis (MS) is a chronic debilitating disease that attacks the central nervous system. This study aims to investigate miR-219 and miR-155-3p expression levels involved in the myelination process following the administration of apamin peptide in the model of multiple sclerosis disease. Forty-four 8 week C57BL/6 male mice (22 ± 5 g) randomly divided into six groups. Apamin (100 µg/kg/BW) was administered intraperitoneally as a co-treatment during phase I (demyelination) or post-treatment phase II (remyelination) twice a week in cuprizone induced MS model. At the end of study myelin content and microRNA expression levels were measured with LFB staining and quantitative Real-Time PCR method, respectively. It was observed that the intended microRNAs were dysregulated during the different phases of disease induction. After 6 weeks of cuprizone exposure, miR-219 downregulated in phase I in comparison with the negative control. On the other hand, the apamin co-treatment significantly inhibit the miR-155-3p upregulation during the phase I as compared with the cuprizone group (p < 0.0001). Apamin has more impact on the miR155-3p reduction in phase I than miR-219 elevation in phase II. It could be considered as a therapeutic option for decreasing plaque formation during the exacerbation phase of the MS disease. Apamin has more impact on the miR155-3p reduction in phase I than miR-219 elevation in phase II. It could be considered as a therapeutic option for decreasing plaque formation during the exacerbation phase of the MS disease.

摘要

多发性硬化症 (MS) 是一种慢性衰弱性疾病,攻击中枢神经系统。本研究旨在探讨米氮平肽给药后参与髓鞘形成过程的 miR-219 和 miR-155-3p 表达水平在多发性硬化症模型中。44 只 8 周龄 C57BL/6 雄性小鼠(22 ± 5 g)随机分为六组。米氮平(100 µg/kg/BW)作为佐剂在杯状蛋白诱导的 MS 模型中在 I 期(脱髓鞘)或 II 期(再髓鞘)两次每周腹腔内给药。研究结束时,通过 LFB 染色和定量实时 PCR 法分别测量髓鞘含量和 microRNA 表达水平。观察到在疾病诱导的不同阶段,预期的 microRNAs 失调。在杯状蛋白暴露 6 周后,miR-219 在 I 期与阴性对照组相比下调。另一方面,与杯状蛋白组相比,米氮平佐剂在 I 期显著抑制 miR-155-3p 的上调(p < 0.0001)。与 II 期 miR-219 升高相比,米氮平对 I 期 miR155-3p 降低的影响更大。它可以被认为是在 MS 疾病恶化阶段减少斑块形成的治疗选择。与 II 期 miR-219 升高相比,米氮平对 I 期 miR155-3p 降低的影响更大。它可以被认为是在 MS 疾病恶化阶段减少斑块形成的治疗选择。

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