Effects of microRNA-338 Transfection into Sciatic Nerve on Rats with Experimental Autoimmune Neuritis

Effects of microRNA-338 Transfection into Sciatic Nerve on Rats with Experimental Autoimmune Neuritis
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microRNA-338转染坐骨神经对实验性自身免疫性神经炎大鼠的影响

DOI:
10.1007/s12031-020-01689-3
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发表时间:
2020-09
影响因子:
3.1
通讯作者:
Qiang Ao
Qiang Ao
中科院分区:
医学4区
文献类型:
--
作者:
Xiaojing Yuan;Yujun Wei;Tianrang Ao;Kai Gong;Qiangsan Sun;Zuncheng Zheng;Haruo Hagiwara;Qiang Ao

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神经脱髓鞘或轴突病变是实验性自身免疫性神经炎 (EAN) 的特征。前期研究表明,microRNA-338可以调节少突胶质细胞和雪旺细胞的分化和成熟,促进大鼠损伤的周围神经。在本研究中,我们在Lewis大鼠EAN模型中使用了microRNA-338编码的慢病毒载体(miR-338-LV),并结合P0肽180-199注射到动物的足垫中以诱导免疫。 miR-338-LV和静脉注射免疫球蛋白(IVIg)(阳性药物)组在疾病高峰期和疾病平台期的临床评分显着优于未治疗组(p<0.05)。在疾病高峰期,miR-338-LV和IVIg组的神经传导速度和复合神经动作电位幅度与未治疗组相比显着增加(p< 0.01)。在疾病高峰期,与未治疗组相比,miR-338-LV 和 IVIg 组的髓磷脂肿胀、空腔形成和片层分离有所改善。与未治疗组相比,miR-338-LV 和 IVIg 组的 S100 和 NF200 表达增加。与未治疗组相比,miR-338-LV和IVIg组的雪旺细胞中Iba1和S100共表达减少,这表明雪旺细胞向炎症细胞的转化减少。总体而言,坐骨神经中的 miR-338-LV 可能通过抑制雪旺细胞转化为炎症细胞来改善 EAN 中的神经肌肉功能。
Nerve demyelination or axonal lesions are characteristic of experimental autoimmune neuritis (EAN). Previous studies have demonstrated that microRNA-338 can regulate the differentiation and maturation of oligodendrocytes and Schwann cells and promote injured peripheral nerves in rats. In this study, we used microRNA-338 coded lentivirus vector (miR-338-LV) in a Lewis rat EAN model, in with the conjunction P0 peptide 180–199 which was injected into the footpads of animals to induce immunization. The clinical scores of miR-338-LV and intravenous immunoglobulin (IVIg) (positive drug) groups were significantly superior to those of untreated group at disease peak and disease plateau (p< 0.05). The nerve conduction velocity and the compound nerve action potential amplitude of miR-338-LV and IVIg groups increased significantly compared to those of the untreated group at disease peak (p< 0.01). At disease peak, myelin swelling, cavity formation, and lamellae separation showed improvement in miR-338-LV and IVIg groups compared to untreated group. S100 and NF200 expression in miR-338-LV and IVIg groups increased compared to that in untreated group. Iba1 and S100 co-expression in Schwann cells in miR-338-LV and IVIg groups decreased compared to that in untreated group, which was indicative of the reduced conversion of Schwann cells into inflammatory cells. Overall, miR-338-LV in sciatic nerves might improve neuromuscular function in EAN by inhibiting the conversion of Schwann cells into inflammatory cells.
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发表时间: 2019
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