[1]许　超　王　娟　刘　锋　梁洁敏　刘伟伟.下调miR-203靶向MEF2C/NF-κB抑制颞叶癫痫大鼠海马胶质细胞的活化和炎症反应[J].中国临床神经外科杂志,2021,26(06):449-454.[doi:10.13798/j.issn.1009-153X.2021.06.013]
　XU Chao,WANG Juan,LIU Feng,et al.Down-regulation of miR-203 inhibits glial cell activation and inflammation in hippocampal tissues of temporal lobe epilepsy rats by targeted regulation of MEF2C/NF-κB pathway[J].,2021,26(06):449-454.[doi:10.13798/j.issn.1009-153X.2021.06.013]
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下调miR-203靶向MEF2C/NF-κB抑制颞叶癫痫大鼠海马胶质细胞的活化和炎症反应()
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《中国临床神经外科杂志》[ISSN:1009-153X/CN:42-1603/TN]

卷:
26
期数:
2021年06期
页码:
449-454
栏目:
实验研究
出版日期:
2021-06-25

文章信息/Info

Title:
Down-regulation of miR-203 inhibits glial cell activation and inflammation in hippocampal tissues of temporal lobe epilepsy rats by targeted regulation of MEF2C/NF-κB pathway
文章编号:
1009-153X（2021）06-0449-06
作者:
许　超　王　娟　刘　锋　梁洁敏　刘伟伟
作者单位：434023 湖北荆州，长江大学医学部（许　超、王　娟、刘　锋、梁洁敏）；434000 湖北荆州，长江大学附属第一医院神经外科（刘伟伟）
Author(s):
XU Chao1;  WANG Juan1;  LIU Feng1;  LIANG Jie-min1;  LIU Wei-wei2.
1. Department of Medicine, Changjiang University, Jingzhou 434023, China; 2. Department of Neurosurgery, The First Affiliated Hospital of Changjiang University, Jingzhou 434000, China
关键词:
颞叶癫痫; miR-203; MEF2C/NF-κB通路; 胶质细胞活化; 炎症反应
Keywords:
Temporal lobe epilepsy;  miR-203;  MEF2C/NF-κB pathway;  Activation of glial cells;  Inflammation
分类号:
R 742.1; Q 786
DOI:
10.13798/j.issn.1009-153X.2021.06.013
文献标志码:
A
摘要:
目的 探讨下调miR-203对颞叶癫痫大鼠海马胶质细胞活化和炎症反应的影响。方法 将46只成年SD大鼠随机分为假手术组（n=10）、模型组（n=12）、阴性对照组（n=12）和miR-203低表达组（n=12）。立体定向辅助下，将海人酸注入大鼠左侧海马CA3区建立颞叶癫痫模型，miR-203低表达组和阴性对照组大鼠左侧海马CA3区分别注射携带miR-203 inhibitor的腺相关病毒和空腺病毒载体，7 d后取左侧海马组织，PCR法检测miR-203水平，ELISA法检测炎症因子[白细胞介素-1β（IL-1β）、IL-6和肿瘤坏死因子α（TNF-α）]水平，免疫印迹法检测肌细胞增强因子2c（MEF2C）、核因子-κB（NF-κB）p65蛋白表达，TUNEL法检测神经元凋亡，GFAP/CD11b/c免疫荧光染色分析胶质细胞活化。结果 模型组大鼠海马组织miR-203、NF-κB p65蛋白表达量、炎症因子（IL-1β、IL-6和TNF-α）水平明显增高（P<0.05），MEF2C蛋白表达量明显降低（P<0.05），活化的胶质细胞数量、神经元凋亡数量明显增多（P<0.05）。双荧光素酶报告基因实验显示，MEF2C是miR-203的靶基因。miR-203表达低表达组大鼠海马组织miR-203表达量、NF-κB p65蛋白表达量、炎症因子（IL-1β、IL-6和TNF-α）水平明显降低（P<0.05），MEF2C蛋白表达量明显增高（P<0.05），活化的胶质细胞数量、神经元凋亡数量明显减少（P<0.05）。结论 下调miR-203，靶向调控MEF2C/NF-κB信号通路，抑制颞叶癫痫大鼠海马胶质细胞的活化、神经元凋亡和炎症反应。
Abstract:
Objective To explore the effect of down-regulation of miR-203 on the glial cell activation and inflammation in hippocampal tissues of temporal lobe epilepsy rats. Methods Forty-six adult SD rats were randomly divided into sham operation group (n=10), model group (n=12), negative control group (n=12) and miR-203 low expression group (n=12). Under stereotactic assistance, kainic acid was injected into the left hippocampus CA3 to establish the temporal lobe epilepsy model. Adeno-associated viral (AAV) integrated with miR-203 inhibitor and AAV vector were injected into the left hippocampal CA3of ??the rats in the miR-203 low expression group and the negative control group, respectively. Seven days after the intervention, the left hippocampal tissues were isolated, and the level of miR-203 was detected by PCR, and the inflammatory factors including interleukin-1β (IL-1β), IL-6 and tumor necrosis factor α (TNF-α) were detected by ELISA, the expression levels of myocyte enhancer factor 2c (MEF2C), nuclear factor-κB (NF-κB) p65 protein were detected by immunoblotting method, neuronal apoptosis was detected by TUNEL method, and glial cell activation was detected by GFAP/CD11b/c immunofluorescence staining. Results In the hippocampal tissues of rats in model group, the expression levels of miR-203 and NF-κB p65 protein, and the levels of inflammatory factors (IL-1β, IL-6 and TNF-α) were significantly increased (P<0.05), and the expression level of MEF2C protein was significantly decreased (P<0.05), the numbers of activated glial cells and apoptic neurons were significantly increased (P<0.05). The dual luciferase reporter gene experiment showed that MEF2C was the target gene of miR-203. In the hippocampal tissues of rats in miR-203 low expression group, the expression levels of miR-203 and NF-κB p65 protein, and the levels of inflammatory factors (IL-1β, IL-6 and TNF-α) were significantly reduced (P<0.05), the protein expression level of MEF2C was significantly increased (P<0.05), and the numbers of activated glial cells and apoptic neurons were significantly reduced (P<0.05). Conclusions Down-regulation of miR-203 inhibits the activation of hippocampal glial cells, neuronal apoptosis and inflammatory response in temporal lobe epilepsy rats, which may be by targeted regulation of the MEF2C/NF-κB signaling pathway.

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备注/Memo

备注/Memo:
通讯作者：刘伟伟，E-mail：guanguan_86@163.com
更新日期/Last Update: 2021-06-25