[关键词]
[摘要]
目的:运用生物信息学方法分析气滞血瘀证差异表达谱,以探索气滞血瘀证可能的生物学基础与发生机制。方法:①检索中国知网和PubMed数据库中气滞血瘀证组学层面研究的相关文献331篇,提取并总结基本资料与RNA差异表达谱;②应用GeneCards数据库进行基因功能注释;③借助DAVID平台对差异表达RNA 进行生物功能与信号通路富集分析;④利用starBase v2.0 平台中的miRNA-target interactions 模块、miRNA-lncRNA interactions 模块、miRNA-circRNA interactions 模块与STRING Version 10.5平台中的Multipleproteins模块建立气滞血瘀证ceRNA-mRNA-protein相互作用网络。结果:①文献分析显示,共有41篇文献报道了气滞血瘀证组学层面研究的结果,其中蛋白表达研究数量最多,其次为mRNA、SNP、miRNA、DNA甲基化、lncRNA、circRNA;②差异表达谱GO功能富集显示,在生物过程方面,气滞血瘀证相关基因主要与细胞对环状化合物的反应、对转录、神经元凋亡基因表达的负性调控以及炎症反应相关;在细胞组成方面,气滞血瘀证相关基因主要与蛋白复合物、核质、细胞表面相关;在分子功能方面,气滞血瘀证相关基因主要与可识别蛋白结合、酶结合、转录调控区域的基因结合相关,其中炎症反应与目前气滞血瘀证生物学基础研究联系最为密切。③差异表达谱KEGG信号通路分析显示,与气滞血瘀证相关基因可能有关的信号通路包括肿瘤相关蛋白多糖、肿瘤坏死因子信号通路、肿瘤相关信号通路、人类T淋巴细胞病毒感染,其中肿瘤坏死因子信号通路与目前气滞血瘀证生物学基础研究联系较为密切。结论:气滞血瘀证相关基因涉及多种生物功能、多条信号通路,其中与炎症反应与肿瘤坏死因子信号通路联系最为密切。
[Key word]
[Abstract]
To analyze the differential expression profiles of qi stagnation and blood stasis syndrome (QSBSS) withbioinformatics method, so as to explore the possible biological basis and mechanism of QSBSS. A total of 331 papers on the study of QSBSS were retrieved in CNKI and PubMed databases, and the basic information as well as RNA differentialexpression profiles were extracted and summarized. The gene function was annotated by GeneCards database, and the Database for Annotation, Visualization and Integrated Discovery (DAVID) was used for enrichment analysis on the biological function and signaling pathway of differentially expressed RNA. The miRNA- target interactions module,miRNA-lncRNA interactions module, miRNA-circRNA interactions module in starBase v2. 0 and the Multiple proteinsmodule in STRING Version 10. 5 were utilized to establish the ceRNA-mRNA-protein interaction network of QSBSS.The literature analysis showed that 41 studies reported the results of QSBSS on omics, in which the number of proteinexpression studies was the most, followed by studies on mRNA, SNP, miRNA, DNA methylation, lncRNA, and circRNA.GO function enrichment analysis of differential expression profiles showed that, firstly, in biological process, QSBSSrelated genes are mainly relevant to cell response to organic cyclic compounds, negative regulation of transcription,negative regulation of neuronal apoptosis gene expression, and inflammatory response. Secondly, in cellular component,QSBSS related genes are mainly relevant to protein complex, nucleoplasm and cell surface. Thirdly, in molecularfunction, QSBSS related genes are mainly relevant to identifiable protein binding, enzyme binding, and the gene bindingin transcriptional regulatory region. Among of them, inflammatory response is the most relevant to the basic biologicalresearch on QSBSS. KEGG signal pathway analysis showed that the signal pathway related to QSBSS related genesincluded proteoglycans in cancer, tumor necrosis factor (TNF) signaling pathway, pathways in cancer, and human Tlymphocyte virus infection. Among of them, the TNF signaling pathway is the most relevant to the basic biologicalresearch on QSBSS. The genes related to QSBSS involve multiple biological functions and multiple signaling pathways.Among of them, the inflammatory response and the TNF signal pathway are the most relevant.
[中图分类号]
[基金项目]
国家中医药管理局公益性行业专项(201207009):证候类中药新药疗效评价方法研究;负责人:王阶;国家自然科学基金委面上基金项目(81673847):冠心病血瘀证相关miRNA表达的甲基化调控机制研究,负责人:王阶。