Screening of Key Genes and Prediction of Drugs for Ischemic Stroke Based on Bioinformatics Approach

YU Yu; WANG Zhong-xing

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Screening of Key Genes and Prediction of Drugs for Ischemic Stroke Based on Bioinformatics Approach

Basic Research | 更新时间：2023-11-01

- Screening of Key Genes and Prediction of Drugs for Ischemic Stroke Based on Bioinformatics Approach
- Journal of Sun Yat-sen University(Medical Sciences) Vol. 42, Issue 1, Pages: 42-50(2021)
- 作者机构：
  
  中山大学附属第一医院麻醉科，广东广州 510080
- 作者简介：
  
  WANG Zhong-xing； E-mail： Doctorwzx@126.com
- 基金信息：
- DOI：
  CLC： R743.4
- Received：03 December 2020，
  
  Published：20 January 2021
- 稿件说明：
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于瑜,王钟兴.基于生物信息学途径筛选缺血性脑卒中关键基因及药物预测[J].中山大学学报（医学科学版）,2021,42(01):42-50.

YU Yu,WANG Zhong-xing.Screening of Key Genes and Prediction of Drugs for Ischemic Stroke Based on Bioinformatics Approach[J].Journal of Sun Yat-sen University(Medical Sciences),2021,42(01):42-50.
于瑜,王钟兴.基于生物信息学途径筛选缺血性脑卒中关键基因及药物预测[J].中山大学学报（医学科学版）,2021,42(01):42-50. DOI：

YU Yu,WANG Zhong-xing.Screening of Key Genes and Prediction of Drugs for Ischemic Stroke Based on Bioinformatics Approach[J].Journal of Sun Yat-sen University(Medical Sciences),2021,42(01):42-50. DOI：

摘要

目的

筛选缺血性脑卒中的关键基因及重要信号通路，预测可能对脑卒中有用的药物。

方法

从GEO数据库下载GSE98319基因芯片数据，该数据包含了假手术组、大脑中动脉梗塞组（MCAO）小鼠的基因芯片检测结果。用R语言的Limma包对数据进行差异表达分析，

0.05且|log

FC|

0.6的基因为差异表达基因。借助STRING网站构建差异表达基因的蛋白质相互作用网络（PPIN）后由Cytoscape软件进行核心子网络筛选及可视化输出。筛选出核心基因后用实时荧光定量PCR（qRT- PCR）验证核心基因在脑缺血小鼠大脑皮层的表达情况。基因集富集分析（GSEA）算法用于京都基因与基因组百科全书（KEGG）和基因本体（GO）富集分析，以FDR

0.05作为富集标准。最后用Connectivity Map数据库预测脑卒中的潜在作用药物。

结果

共筛出521个差异mRNA，其中421个上调、100个下调，其中2个关键基因

Drd4

（

=0.000 019）和

Hcar2

（

=0.000 094）经qRT-PCR实验证实在脑缺血后表达均升高。4种小分子化合物艾司洛尔（Esmolol）、甲巯咪唑（Methimazole）、吐根酚碱（Cephaeline）、水仙环素（Narciclasine）可能对缺血性卒中有治疗作用。

结论

Drd4

和

Hcar2

可能与缺血性卒中的发生发展密切相关。预测出的4种药物可为后续药物研究提供参考。

Abstract

Objective

To screen out key genes and important signal pathways of ischemic stroke to predict potential drugs that might be useful for stroke.

Methods

We obtained GSE98319 Microarray data from GEO database which contained sequencing results from control （Sham group） and experimental （middle cerebral artery occlusion， MCAO） mice. Limma package of R language was used to analyze Microarray data. Differentially expressed genes were selected with

0.05 and |log

FC|

0.6 as the criteria. Protein-Protein Interaction Network （PPIN） of differentially expressed genes was constructed by STRING online website and visualized by Cytoscape software. Quantitative real-time polymerase chain reaction（qRT-PCR）was performed to testify hub genes expression level. Gene Set enrichment analysis （GSEA） algorithm was used in functional enrichment analysis of Kyoto Encyclopedia of Genes and Genomics （KEGG） and Gene Ontology （GO） with FDR

0.05 as the enrichment standard. Finally， potential agents for stroke were predicted by Connectivity Map.

Results

A total of 521 differentially expressed genes were identified， 421 up-regulated and 100 down-regulated. Two hub genes：

Drd4

（

=0.000 019）and

Hcar2

（

=0.000 094）expression level upregulated in stroke mice cortex validated by qRT- PCR. Finally， four small molecule compounds：Esmolol， Methimazole， Cephaeline and Narciclasine were predicted to have potential therapeutic effects on ischemic stroke.

Conclusions

Drd4

and

Hcar2

may be closely related to the occurrence and development of ischemic stroke. Four potential therapeutic drugs are predicted， providing reference for the subsequent research on drug therapy.

关键词

Keywords

references

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Related Institution

Sun Yat-sen Memorial Hospital，Sun Yat-sen University

Rehabilitation Center of The First Affiliated Hospital of Henan University of Traditional Chinese Medicine

Henan University of Traditional Chinese Medicine， School of Rehabilitation Medicine

Rehabilitation Center ， The First Affiliated Hospital， Henan University of Traditional Chinese Medicine

School of Rehabilitation Medicine， Henan University of Traditional Chinese Medicine

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