Downregulation of MicroRNA-199a-5p Alleviated Lidocaine-Induced Sensory Dysfunction and Spinal Cord Myelin Lesions in a Rat Model,Toxicology Letters

当前位置： X-MOL 学术 › Toxicol. Lett. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Downregulation of MicroRNA-199a-5p Alleviated Lidocaine-Induced Sensory Dysfunction and Spinal Cord Myelin Lesions in a Rat Model
Toxicology Letters ( IF 2.9 ) Pub Date : 2021-01-01 , DOI: 10.1016/j.toxlet.2020.11.001
Zhong Zhang ₁ , Jian Wang ₁ , Zongbin Song ₁ , Yunjiao Wang ₁ , Zhigang Cheng ₁ , Qulian Guo ₁ , E Wang ₁ , Yanping Jian ₁ , Lei Wu ₂

Affiliation

Lidocaine induces neurotoxicity in the spinal cord, but the underlying mechanisms remain unclear. In this study, we evaluated the effects of miR-199a-5p on 10% lidocaine neurotoxicity. Increased expression of miR-199a-5p in the spinal cord of rats treated with 10% lidocaine was assessed by qRT-PCR. Furthermore, after miR-199a-5p antagomir administration, the sensory dysfunction and myelin sheath lesions (evaluated by semithin sections stained with toluidine blue, electron microscopy, g-ratios and myelin thickness) induced by 10% lidocaine were alleviated. Myelin regulatory factor (MYRF), a key molecule of myelin sheath development, was predicted to be a target gene of miR-199a-5p by the TargetScan and miRBase databases. MYRF and its downstream factors myelin basic protein (MBP), proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG) were significantly decreased after intrathecal 10% lidocaine administration. Moreover, these changes were reversed after miR-199a-5p antagomir administration. FISH-immunofluorescence showed coexpression of miR-199a-5p and MYRF in the spinal cord white matter of rats. A luciferase reporter assay further demonstrated the functional association between miR-199a-5p and MYRF. Overall, miR-199a-5p upregulation is involved in 10% lidocaine-induced spinal cord toxicity through regulation of MYRF. Therefore, downregulating miR-199a-5p expression may be a potential strategy to ameliorate spinal cord neurotoxicity induced by 10% lidocaine.

中文翻译：

MicroRNA-199a-5p 的下调可减轻大鼠模型中利多卡因引起的感觉功能障碍和脊髓髓鞘病变

利多卡因会引起脊髓神经毒性，但其潜在机制仍不清楚。在本研究中，我们评估了 miR-199a-5p 对 10% 利多卡因神经毒性的影响。通过 qRT-PCR 评估用 10% 利多卡因治疗的大鼠脊髓中 miR-199a-5p 表达的增加。此外，给予miR-199a-5p antagomir后，10%利多卡因诱导的感觉功能障碍和髓鞘病变（通过甲苯胺蓝染色的半薄切片、电镜、g比和髓鞘厚度进行评估）得到缓解。髓鞘调节因子（MYRF）是髓鞘发育的关键分子，TargetScan和miRBase数据库预测其是miR-199a-5p的靶基因。鞘内注射10%利多卡因后，MYRF及其下游因子髓鞘碱性蛋白（MBP）、蛋白脂质蛋白（PLP）和髓鞘少突胶质细胞糖蛋白（MOG）显着降低。此外，给予 miR-199a-5p antagomir 后，这些变化被逆转。 FISH 免疫荧光显示大鼠脊髓白质中 miR-199a-5p 和 MYRF 共表达。荧光素酶报告基因测定进一步证明了 miR-199a-5p 和 MYRF 之间的功能关联。总体而言，miR-199a-5p 上调通过调节 MYRF 参与 10% 利多卡因诱导的脊髓毒性。因此，下调miR-199a-5p表达可能是改善10%利多卡因诱导的脊髓神经毒性的潜在策略。

更新日期：2021-01-01

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11