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Received:March 22, 2020 Published Online:November 20, 2020
Received:March 22, 2020 Published Online:November 20, 2020
中文摘要: 目的 应用整合医学理论的思维探寻在蛛网膜下腔出血(SAH)后脑、心、肝、肺、肾组织中特异性基因的变化。方法 在高通量基因表达数据库(GEO)中搜索出脑、心、肝、肾、肺的特异性基因,特异性基因的筛选应用Bioconductor的微阵列数据中的标记基因查找器(MGFM)计算出基因的特异值(0～1),来源数据库序列号为GSE3526、GSE1133、GSE2361、GDS596。SAH靶点应用比较毒理基因组学数据库(CTD)、在线人类孟德尔遗传数据库(OMIM)、治疗靶标数据库(TTD)、遗传药理学与药物基因组学数据库(Pharm GKB)进行检索,去重、取并集后,即为相关SAH靶点库。关键靶点筛选及富集应用Cytoscape(Version 3.7.1)的Merge及Genemania插件。结果 SAH疾病靶点269个。筛选出脑、心、肝、肺、肾的特异性基因分别为1 434、321、497、653、270个,与SAH比对后得出的关键靶点分别为39、8、27、23、7个。Genemania扩增关键靶点后得到分子功能的基因本体(GO)富集图及相应的Q值表明,（1）SAH后心脏特异性基因改变主要与血管内皮生长因子受体信号传导通路及血小板α颗粒的释放等有关;(2)肝脏主要与药物的分解代谢及单加氧酶的活性等有关;(3)肺脏主要与TOLL样受体2、3、4、5、9、10亚型的传导通路有关;(4)脑主要与意识状态、记忆等高级功能有关;(5)肾脏的特异性基因与血压调节有关。结论 SAH后心、肝、肺组织特异性基因改变最为显著。这些重要器官的功能改变量化了机体在病理状态下各器官反应的统一性。SAH后脑、心、肝、肺、肾器官及其特异性基因的改变可为深入探究藏象模型理论提供新的思路与方法。
Abstract:Objective To explore the changes of specific genes in the brain,heart,liver,lung and kidney after subarachnoid hemorrhage (SAH) using the idea of integrated medicine theory.Methods Specific genes of the brain,heart,liver,kidney and lung were searched out in Gene Expression Omnibus (GEO),and gene specificity values (0-1) were calculated by using MGFM of Bioconductor.The IDs of the source databases were GSE3526,GSE1133,GSE2361 and GDS596.Target genes of SAH were searched in Comparative Toxicogenomics Database (CTD),Online Mendelian Inheritance in Man(OMIM),herapeutic Target Database(TTD) and Pharmacogenetics and Pharmacogenomics Knowledge Base(Pharm GKB),which were treated by removing duplicates and incorporating.The Merge and Genemania plug-ins of Cytoscape (Version 3.7.1) were applied for key targets′ screening and enrichment.Results The number of target genes of SAH was 269.The specific genes of brain,heart,liver,lung and kidney were screened out to be 1 434,321,497,653 and 270,respectively.After comparison with SAH,the key targets were 39,8,27,23 and 7,respectively.After analysis of the key targets by Genemania,the GO enrichment and Q-value were obtained,which showed that (1)the cardiac-specific genes after SAH were mainly related to the vascular endothelial growth factor receptor signaling pathway and the release of platelet granules;(2)the liver-specific genes were mainly related to the catabolism of drugs and the activity of monooxygenase;(3)the lung-specific genes are mainly associated with 2,3,4,5,9 and 10 Toll-like receptors;(4)the brain-specific genes were mainly concerned with the functions of consciousness and memory;(5)the kidney-specific genes were involved in blood pressure regulation.Conclusions The specific genes of heart,liver and lung are the most significant ones after SAH.The specific gene changes of these vital organs can quantify the unity of organs′ responses under pathological conditions,which provide new ideas and methods for in-depth exploration of the theory of Zangxiang model.
keywords: Subarachnoid hemorrhage Integrative medicine Tissue-specific gene Gene Expression Omnibus
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基金项目:国家自然科学基金面上项目(81971133,81671174);辽宁省科学技术计划项目(20180550504)
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