基于文献的气滞血瘀证差异表达谱生物信息学研究
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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Multiple proteins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。
To analyze the differential expression profiles of qi stagnation and blood stasis syndrome(QSBSS) with bioinformatics 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 differential expression 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 proteins module 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 protein expression 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, QSBSS related 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 molecular function, QSBSS related genes are mainly relevant to identifiable protein binding, enzyme binding, and the gene binding in transcriptional regulatory region. Among of them, inflammatory response is the most relevant to the basic biological research on QSBSS. KEGG signal pathway analysis showed that the signal pathway related to QSBSS related genes included proteoglycans in cancer, tumor necrosis factor(TNF) signaling pathway, pathways in cancer, and human T lymphocyte virus infection. Among of them, the TNF signaling pathway is the most relevant to the basic biological research 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.
To analyze the differential expression profiles of qi stagnation and blood stasis syndrome(QSBSS) with bioinformatics 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 differential expression 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 proteins module 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 protein expression 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, QSBSS related 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 molecular function, QSBSS related genes are mainly relevant to identifiable protein binding, enzyme binding, and the gene binding in transcriptional regulatory region. Among of them, inflammatory response is the most relevant to the basic biological research on QSBSS. KEGG signal pathway analysis showed that the signal pathway related to QSBSS related genes included proteoglycans in cancer, tumor necrosis factor(TNF) signaling pathway, pathways in cancer, and human T lymphocyte virus infection. Among of them, the TNF signaling pathway is the most relevant to the basic biological research 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.
引文
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27崔同建,陈义乾,戴永美,等.大肠癌中医证型与ERCC1基因多态性的相关研究.中国中西医结合杂志,2012,32(5):628-632.
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2姚乃礼.中医证候鉴别诊断学.北京:人民卫生出版社,2002:123.
3国家中医药管理局.中药新药临床研究指导原则.北京:中国医药科技出版社,2002.
4高嘉良.气滞血瘀证诊断量表及其circRNA差异表达研究.北京:中国中医科学院博士学位论文,2017.
5梁耀月,董世芬,程龙,等.气滞血瘀证大鼠舌部基因表达谱变化初探.中国比较医学杂志,2017,27(9):11-16.
6邵丽娟.DLL4在胃癌中的表达及与中医证相关性研究.扬州大学,2017.
7刘辉艳.基于microRNA表达谱的变化探讨活血消异方治疗子宫内膜异位症疗效机制研究.北京:中国中医科学院博士学位论文,2017.
8沈智杰,陈骁康,王英杰,等.229例急性冠脉综合征氯吡格雷抵抗患者CYP2C19基因多态性与中医证型分布的相关性.中国中西医结合杂志,2017,37(3):291-296.
9乔磊,王海芹.自拟溃灵汤灌肠治疗气滞血瘀型重症溃疡性结肠炎的疗效及对肠黏膜组织中IL-8和NF-κB mRNA表达的影响.中医药信息,2017,34(4):98-101.
10蒋雨薇.RPL23、MDM2的表达与胃癌中医证型的相关性研究.武汉:湖北中医药大学,硕士学位论文,2016.
11崔飞飞.不同辨证分型的晚期三阴乳腺癌免疫及miRNA特点及辨证中药临床疗效.北京:北京中医药大学硕士论文,2016.
12向忠军.基于甲基化修饰探讨加减养心通脉方对冠心病血瘀证及亚型CTNNB1、DES基因表达的影响研究.长沙:湖南中医药大学硕士学位论文,2015.
13王雨村,刘宏斌.胃癌中医证型与C-erbB-2表达水平的相关性研究.医学研究杂志,2016,45(8):109-113.
14宁天一,程嘉艺,王婷婷.血府逐瘀汤对不可预见性刺激致血瘀的作用及机制.中国实验方剂学杂志,2016(4):110-114.
15 He L,Fang M,Chen L,et al.Transcriptome analysis of blood stasis syndrome in subjects with hypertension.中医杂志(英文版),2016,36(2):173-180.
16邵静,朱晓萌.不稳定型心绞痛患者血管紧张素转换酶基因多态性与中医证型及冠状动脉斑块性质的关系.中医杂志,2015,56(19):1671-1674.
17程荣菲,武哲丽.肝癌中医证型与DLC-1基因甲基化表达的相关性研究,2015(2):64-67.
18何铃,方梅霞,陈利国,等.高血压病血瘀证相关miRNA的筛选.中国病理生理杂志,2015,31(5):817-822.
19魏艺.老老年高血压病中医证候流行病学特征及LncRNA表达谱研究.北京:中国中医科学院博士学位论文,2015.
20徐建军,过建春,蔡兆斌,等.TGF-β1基因多态性与慢性乙肝肝纤维化中医证型的相关性探讨.浙江中医杂志,2014,49(5):313-314.
21 Hou J,Wang J,Lin C,et al.Circulating microRNA profiles differ between qi-stagnation and qi-deficiency in coronary heart disease patients with blood Stasis syndrome.Evidence-Based Complementray and Alternative Medicine,2014,(2014-12-4):926962.
22于立友,汪龙德,张晶,等.化纤保肝方治疗气滞血瘀型肝纤维化的临床研究.西部中医药,2013(10):84-87.
23李国威.胃癌中医证型与P53、VEGF表达水平相关性研究.西安:陕西中医学院硕士学位论文,2013.
24文怡.子宫内膜异位症血瘀证差异蛋白质组学研究.成都中医药大学,2013.
25宁天一,王婷婷,姜静,等.气滞血瘀证大鼠NO/NOS体系的变化.世界中医药,2013,8(1):71-73.
26蒋卫民,朱长乐,刘健,等.212例高脂血症患者中医证候特点与ApoE基因多态性的相关性分析.中华中医药杂志,2012(5):1458-1460.
27崔同建,陈义乾,戴永美,等.大肠癌中医证型与ERCC1基因多态性的相关研究.中国中西医结合杂志,2012,32(5):628-632.
28宁天一,王婷婷,程嘉艺.气滞血瘀证大鼠H2S/CSE、CBS体系的变化.中药药理与临床,2012,28(5):234-237.
29黄金燕.人子宫内膜异位症血瘀证在位内膜差异蛋白质组学及免疫组化研究.成都:成都中医药大学博士学位论文,2012.
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