miR-145-5p/Nurr1/TNF-a轴信号在大鼠脑缺血再灌注损伤的调控作用研究
发布时间：2021-11-28 01:20
背景:脑卒中是严重威胁着人类的生命健康的重大疾病之一。Nurr1是核受体4家族的一个成员。Nurr1在炎症反应中明显下调且参与帕金森疾病中神经元的死亡。microRNAs在脑缺血再灌注损伤中发挥重要作用参与多种关键因子的转录水平的调节。Nurr1的异常表达与多种信号通路相关有,但miRNA与Nurr1的调节关系在脑缺血再灌注损伤中几乎未见报道。目的:本研究目的在于:（1）在体内和体外实验探索Nurr1在脑缺血再灌注损伤中的表达情况及Nurr1相关的microRNAs;（2）在体内和体外实验探索Nurr1蛋白的转录后调控网络,及其在活化的胶质细胞的具体作用机制;（3）探究miR-145-5p/Nurr1/TNF-a轴信号在大鼠脑缺血再灌注损伤中的具体功能。方法:（1）原代神经元细胞和小胶质细胞培养。（2）神经元细胞与小胶质细胞共培养模型建立及OGD/R实验。（3）大鼠大脑中动脉梗塞再灌注（MCAO/R）模型构建,神经功能学结果与梗塞体积分析。（4）RNA提取,逆转录和实时定量qPCR。（5）大鼠侧脑室注射miR-145-5p mimic和miR-145-5p antagomir。（6）N...
【文章来源】：重庆医科大学重庆市
【文章页数】：81 页
【学位级别】：博士
【部分图文】：
MCAO模型后，TTC染色
(8)检测 Nurr1 3’UTR 片段与 miRNA 结合情况的对照实验分组：第一组 pMIR-质粒不加 Nurr1 3’UTR 片段 + miRNA图 2 HEK293T 细胞中 miR145-5p 与 Nurr1 3’UTR 片段结合的预实
47图 4 直接靶向 Nurr1 3′ UTR 的 miRNAs 筛选Figure 4 Screening for miRNAs that directly target the 3′UTR of Nurr1.(A) The infarct volume was negatively correlated with Nurr1 expression some extent byPearson correlation test, but was not statistically significant (correlation coefficient -0.457, P =0.362). (B) Heat map of predicted miRNAs expression in cerebral cortex tissue from sham andMCAO/R animals (one-way ANOVA, p < 0.05). (C) The predicted binding sites of selected miRNA(in green color) to the 3'UTR of Nurr1 (in red color) is mapped in this figure. Nucleotides whichwere altered for mutational studies are marked in gray color of background. (D) Quantitation of th
【参考文献】：
期刊论文
[1]Novel splicing variant of the human orphan nuclear receptor Nurr1 gene[J]. 徐评议,乐卫东. Chinese Medical Journal. 2004(06)
本文编号：3523408
【文章来源】：重庆医科大学重庆市
【文章页数】：81 页
【学位级别】：博士
【部分图文】：
MCAO模型后，TTC染色
(8)检测 Nurr1 3’UTR 片段与 miRNA 结合情况的对照实验分组：第一组 pMIR-质粒不加 Nurr1 3’UTR 片段 + miRNA图 2 HEK293T 细胞中 miR145-5p 与 Nurr1 3’UTR 片段结合的预实
47图 4 直接靶向 Nurr1 3′ UTR 的 miRNAs 筛选Figure 4 Screening for miRNAs that directly target the 3′UTR of Nurr1.(A) The infarct volume was negatively correlated with Nurr1 expression some extent byPearson correlation test, but was not statistically significant (correlation coefficient -0.457, P =0.362). (B) Heat map of predicted miRNAs expression in cerebral cortex tissue from sham andMCAO/R animals (one-way ANOVA, p < 0.05). (C) The predicted binding sites of selected miRNA(in green color) to the 3'UTR of Nurr1 (in red color) is mapped in this figure. Nucleotides whichwere altered for mutational studies are marked in gray color of background. (D) Quantitation of th
【参考文献】：
期刊论文
[1]Novel splicing variant of the human orphan nuclear receptor Nurr1 gene[J]. 徐评议,乐卫东. Chinese Medical Journal. 2004(06)
本文编号：3523408
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