[1]柯伟 邓小容 李文澜 张兆辉.MicroRNA-18a靶向性干预对减轻永久性大脑中动脉闭塞所致小鼠脑梗死的实验研究[J].卒中与神经疾病杂志,2019,26(05):518-521.[doi:10.3969/j.issn.1007-0478.2019.05.003]
　Ke Wei,Deng Xiaorong,Li Wenlan,et al.Experimental study of MicroRNA-18a targeted intervention in reducing the injury of permanent middle cerebral artery occlusion in mice[J].Stroke and Nervous Diseases,2019,26(05):518-521.[doi:10.3969/j.issn.1007-0478.2019.05.003]
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MicroRNA-18a靶向性干预对减轻永久性大脑中动脉闭塞所致小鼠脑梗死的实验研究()
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《卒中与神经疾病》杂志[ISSN:1007-0478/CN:42-1402/R]

卷:
第26卷
期数:
2019年05期
页码:
518-521
栏目:
论 著
出版日期:
2019-10-20

文章信息/Info

Title:
Experimental study of MicroRNA-18a targeted intervention in reducing the injury of permanent middle cerebral artery occlusion in mice
文章编号:
1007-0478(2019)05-0518-05
作者:
柯伟 邓小容 李文澜 张兆辉
430060 武汉大学人民医院神经内科(柯伟 张兆辉),麻醉科[李文澜(通信作者)]; 湖北省第三人民医院神经内科(邓小容)
Author(s):
Ke Wei※; Deng Xiaorong; Li Wenlan; et al.※
Department of Neurology,Renmin Hospital of Wuhan University, Wuhan 430060
关键词:
大脑中动脉闭塞 miR-18a 失调蛋1(ATXN1)糖氧剥夺 PC12细胞
Keywords:
Middle cerebral artery occlusion miR-18a ATXN1 Oxygen-glucose deprivation PC12 cells
分类号:
R743.3
DOI:
10.3969/j.issn.1007-0478.2019.05.003
文献标志码:
A
摘要:
目的 探讨RNA-18a在脑梗死中的作用。方法 在糖氧剥夺后通过qRT-PCR方法分析miR-18a的表达水平,通过Western blot 和 qRT-PCR方法检测ATXN1表达水平。MiR-18a mimics转移到PC12内上调miR-18a的表达; miR-18a的目标是预测生物学信息并用萤光素酶报告基因分析证实; 大脑中动脉闭塞1 h后把Agomir-18a注射入脑室内; 大脑中动脉闭塞24 h后评估脑梗死体积、神经功能缺损评分和LDH水平。结果 与常氧组比较,缺氧组PC12细胞内miR-18a的表达水平明显下调,ATXN1 mRNA和蛋白的表达水平明显升高。萤光素酶报告基因分析提示miR-18a 直接作用ATXN1,而且当PC12转染miR-18a mimics 时ATXN1表达水平明显增高。此外,注入miR-18a激动剂24 h后脑梗死体积显著减小,同样的改变表现在神经功能缺损评分和LDH水平。结论 miR-18a可以缓解大脑中动脉永久性闭塞和ATXN1所致的脑损伤,miR-18a激动剂或许可以作为一种有效的治疗脑梗死的方法。
Abstract:
ObjectiveTo investigate the role of miR-18a in cerebral infarction.Methods qRT-PCR was used to analyze the expression level of miR-18a after oxygen-glucose deprivation in PC12.ATXN1 expression level was detected by Western blot and qRT-PCR.MiR-18a mimics was transferred into PC12 cells for up-regulated miR-18a expression level.The target of miR-18a was predicted by bioinformatic analysis and conrmed by luciferase reporter assay.Agomir-18a was injected into intracerebroventricular of mice after 1 h of middle cerebral artery occlusion(MCAO).Brain infarct volume,neurological decit score and the LDH level in ischemia brain was assessed in mice subjected to 24 h of MCAO.Results The expression level of miR-18a in PC12 was remarkably down-regulated after subjected to hypoxia,while ATXN1 mRNA and protein expression level under hypoxic conditions were signicant higher compared with normoxia.Luciferase reporter analysis indicated that ATXN1 was a direct target of miR-18a.Furthermore,the protein and mRNA levels of ATXN1 was dramatically increased when PC12 was transfected with miR-18a mimics.Moreover,post-injected with miR-18a agomir,the brain infarct volume was greatly decreased after 24 h of MCAO,the same change were found in neurological decit score and the LDH level in brain ischemic mice.Conclusion miR-18a alleviated the injury induced by permanent MCAO in mice by targeting ATXN1.Post-treatment with miR-18a agomir might be an effective new approach for stroke therapy.

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备注/Memo

备注/Memo:
(2019-04-20收稿 2019-05-30修回)
更新日期/Last Update: 2019-10-20