天津医药

天津医药 ›› 2017, Vol. 45 ›› Issue (4): 355-358.doi: 10.11958/20170062

• 细胞与分子生物学 • 上一篇    下一篇

实验性蛛网膜下腔出血后脑动脉的基因 表达谱及功能分析

甘宁 1， 潘勤 1， 刘思思 1， 任可 2， 周帅 3， 董海青 1， 宋朝彦 1， 王毅 3△   

  1. 1 保定市第一中心医院总院神经外科 （邮编 071000）； 2 吉林大学药学院； 3 天津医科大学总医院神经外科， 天津市神经病学研 究所
  • 收稿日期:2017-01-12 修回日期:2017-02-21 出版日期:2017-04-15 发布日期:2017-04-15
  • 通讯作者: △通讯作者 E-mail: sinuosiwo@sina.com E-mail:jiyilide2000@sina.com
  • 作者简介:甘宁 （1980）， 男， 主治医师， 硕士学位， 主要从事神经外科学研究
  • 基金资助:
    天津市应用基础与前沿技术研究计划 （青年项目）（15JCQNJC11300）

Gene expression profiling and functional analysis of cerebral artery after experimental subarachnoid hemorrhage

GAN Ning1, PAN Qin1, LIU Si-si1, REN Ke2, ZHOU Shuai3, DONG Hai-qing1, SONG Zhao-yan1, WANG Yi3△   

  1. 1 Department of Neurosurgery, General Division, The First Central Hospital of Baoding, Baoding 071000, China; 2 Jilin University School of Pharmacy Sciences; 3 Department of Neurosurgery, Tianjin Medical University General Hospital; Tianjin Institute of Neurology
  • Received:2017-01-12 Revised:2017-02-21 Published:2017-04-15 Online:2017-04-15
  • Contact: △Corresponding Author E-mail: sinuosiwo@sina.com E-mail:jiyilide2000@sina.com

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摘要： 目的 探讨兔蛛网膜下腔出血 （SAH） 后脑血管痉挛 （CVS） 基底动脉和正常基底动脉基因表达的差异。方 法 兔 SAH 模型脑基底动脉及正常兔脑基底动脉的 cDNA 基因芯片下载于 GEO 数据库。使用 Bioconductor 软件 对芯片进行分析筛选， 并用 Cytoscape 软件对差异表达基因进行功能富集和信号通路分析。随后选取成年雄性日本 大耳兔 6 只， 随机分为正常对照组 （n=3） 和 SAH 模型组 （n=3）。采用枕大池二次注血法复制兔 SAH 模型， 取第 0 天 未行手术处理的对照兔基底动脉标本 RNA 和第 5 天 SAH 后基底动脉标本 RNA 行 qRT-PCR， 验证部分差异基因。 结果 在兔正常基底动脉和兔 SAH 模型基底动脉中共获得 4 356 个差异表达的基因， 其中 920 个差异表达基因 （P＜0.05）， 如 GRIK1、 MYH13、 ZNF45、 SAA3、 RLN1、 MSR1 等。功能富集分析结果显示差异表达基因涉及钙离子跨 膜转运蛋白活性调节、 离子跨膜转运负调控、 钾离子转运调控、 JAK-STAT 信号通路级联的正调节等相关生物学过 程。通路分析显示这些基因与钙信号通路、 cGMP-PKG 信号通路、 HIF-1 信号通路、 PI3K-Akt 信号通路等有关。 qRT-PCR 验证表明 SAH 模型组 MSR1 下调， 与芯片结果一致。结论 兔造模后 CVS 基底动脉中存在基因的差异 化表达， 并且 MSR1 基因可以作为研究 CVS 病理机制的潜在靶点。

关键词: 蛛网膜下腔出血, 血管痉挛, 颅内, 基底动脉, 寡核苷酸序列分析, GO 分析, 通路分析

Abstract: Objective To explore the difference of gene expression profiling between normal basilar arteries and basilar arteries of cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) in rabbits. Methods cDNA chip of normal basilar arteries and basilar arteries of CVS after SAH in rabbits were downloaded from GEO database. The chip was analyzed and screened by Bioconductor software, and function enrichment and pathway analysis of the differentially expressed genes were analyzed by Cytoscape software. Then 6 adult male Japanese rabbits were used, and randomly divided into normal control group (n=3) and SAH model group (n=3). Rabbit SAH models were established by cisterna secondaryblood-injection method. RNA data of normal basilar artery specimens on the 0 day and basilar artery specimens after SAH on the 5- day were used to validate the parts of differentially expressed genes by qRT- PCR. Results A total of 4 356 differentially expressed genes were found in normal basilar arteries and basilar arteries of CVS after SAH in rabbits. Among them, 920 genes were considered to be significant with P- value＜0.05, such as GRIK1, MYH13, ZNF45, SAA3, RLN1, MSR1 and others. Function enrichment analysis indicated that the differentially expressed genes were involved in regulation of Ca2 + transmembrane transporter activity, negative regulation of ion transmembrane transport, regulation of potassium ion transport, positive regulation of JAK-STAT signaling cascades and other biological processes. Pathway analysis showed that calcium signaling pathway, cGMP- PKG signaling pathway, HIF- 1 signaling pathway, PI3K- Akt signaling pathway and other signaling pathways maybe related with the differentially expressed genes. qRT- PCR verification showed that the expression of MSR1 in SAH model group was consistent with that of the chip result. Conclusion The gene expressions of basilar arteries of CVS after SAH in rabbits are significantly different, and MSR1 gene can be used as a potential target for studying the pathological mechanism of CVS.

Key words: subarachnoid hemorrhage, vasospasm, intracranial, basilar artery, oligonucleotide array sequence analysis, GO analysis, pathway analysis