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Hydroxychloroquine effects on miR-155-3p and miR-219 expression changes in animal model of multiple sclerosis.
Metabolic Brain Disease ( IF 3.2 ) Pub Date : 2020-08-29 , DOI: 10.1007/s11011-020-00609-z
Fatemeh Mazloumfard 1 , Mina Mirian 2 , Seyed-Mehdi Eftekhari 3 , Mehdi Aliomrani 4
Affiliation  

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system which causes chronic demyelination. Hydroxychloroquine (HCQ) possess immunosuppressive and anti-inflammatory properties. The aim of this study was to investigate the effect of HCQ on miR-219 and miR-155-3p expression changes in MS-induced model. The animal model was induced by the administration of cuprizone containing food pellets (0.2%). Briefly, C57BL/6 mice were randomly divided into five groups. Group 1 received normal food and water during the study. Group 2 received cuprizone pellets for 5 weeks (demyelination phase) following one-week normal feeding during the remyelination phase. The remaining three groups received HCQ (2.5, 10 and 100 mg/kg) via drinking water during the demyelination phase. At the end of each phase, mice were deeply anesthetized, perfused with PBS through the heart, and their brains were removed. Brain sections stained with luxol fast blue and the images were analyzed. Also, the expression levels of miR-219 and miR-155-3p were evaluated by quantitative Real-Time PCR in all samples. HCQ decreased the expression of miR-155-3p and increased miR-219 expression in animals treated with 100 mg/kg of HCQ compared to the control group (p < 0.0001) and the cuprizone group (p < 0.0001). LFB method revealed a gradual increment of myelination in animals treated with 10 and 100 mg/kg of HCQ compared to the cuprizone group. Based on the obtained results of this study, HCQ can decrease microglial activity and increase oligodendrocye production by altering the expression of disease-associated miRNAs.



中文翻译:

羟氯喹对多发性硬化动物模型中 miR-155-3p 和 miR-219 表达变化的影响。

多发性硬化症 (MS) 是一种导致慢性脱髓鞘的中枢神经系统慢性炎症性疾病。羟氯喹 (HCQ) 具有免疫抑制和抗炎特性。本研究的目的是研究 HCQ 对 MS 诱导模型中 miR-219 和 miR-155-3p 表达变化的影响。通过给予含铜宗的食物颗粒 (0.2%) 来诱导动物模型。简而言之,C57BL/6 小鼠随机分为五组。第 1 组在研究期间接受正常的食物和水。第 2 组在髓鞘再生阶段正常喂养 1 周后接受 5 周(脱髓鞘阶段)铜宗丸。其余三组在脱髓鞘阶段通过饮用水接受 HCQ(2.5、10 和 100 mg/kg)。在每个阶段结束时,小鼠被深度麻醉,用 PBS 通过心脏灌注,并取出他们的大脑。脑切片用 luxol fast blue 染色并分析图像。此外,通过定量实时 PCR 评估了所有样品中 miR-219 和 miR-155-3p 的表达水平。与对照组相比,HCQ 在用 100 mg/kg HCQ 治疗的动物中降低了 miR-155-3p 的表达并增加了 miR-219 表达。p  < 0.0001) 和铜宗组 ( p  < 0.0001)。LFB 方法显示,与铜宗组相比,用 10 和 100 毫克/千克 HCQ 治疗的动物髓鞘形成逐渐增加。根据本研究获得的结果,HCQ 可以通过改变疾病相关 miRNA 的表达来降低小胶质细胞活性并增加少突胶质细胞的产生。

更新日期:2020-08-29
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