文章摘要
王璐,饶颖,周佳林,等.基于数据挖掘和网络药理学对腹泻型肠易激综合征的方证探讨[J].浙江中医药大学学报,2022,46(9):1043-1054.
基于数据挖掘和网络药理学对腹泻型肠易激综合征的方证探讨
Research on Prescriptions and Syndromes of Irritable Bowel Syndrome with Predominant Diarrhea Based on Data Mining and Network Pharmacology
DOI:10.16466/j.issn1005-5509.2022.09.021
中文关键词: 腹泻型肠易激综合征  中医学  数据挖掘  网络药理学  作用机制  方证  靶点  信号通路
英文关键词: irtable bowel syndrome with predominant diarrhex  traditional Chinese medicine  data mining network pharmaology  mech-anism of action  prescription and syndrome  targcts  signalig pathway
基金项目:江西省卫生健康委科技计划项目(202210800)
作者单位
王璐 江西中医药大学 南昌 330000 
饶颖 江西中医药大学 南昌 330000 
周佳林 江西中医药大学 南昌 330000 
戴琦 江西中医药大学附属医院
江西省中医消化病临床研究基地 
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中文摘要:
      [目的] 以数据挖掘和网络药理学为基础,探讨中药治疗腹泻型肠易激综合征(irritable bowel syndrome with predominant diarrhea,IBS-D)的方证关系。[方法] 收集中国知网(China National Knowledge Infrastructure,CNKI)、中国生物医学文献服务系统(Chinese Biomedical Literature Service system,SinoMed)、万方期刊数据库(Wanfang Database)、维普中文期刊数据库(VIP Database for Chinese Technical Periodicals)从建库至2020年12月所有关于脾虚湿盛型和脾肾阳虚型IBS-D的文献,提取相关方药信息后,应用WPS Office Excel、IBM SPSS Modeler 18.1软件进行频数分析和关联规则分析,得到核心中药配伍。通过中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)、中医药百科全书(The Encyclopedia of Traditional Chinese Medicine,ETCM)数据库、UniProt数据库获取核心中药的有效成分和作用靶点,通过基因疾病关联数据库(Gene-Disease Association Database,DisGeNET)、人类基因综合数据库(Human Gene Comprehensive Database,GeneCards)、人类孟德尔遗传在线(Online Mendelian Inheritance in Man,OMIM)数据库获取疾病靶点,对中药靶点和疾病靶点进行交集分析,将所得结果导入STRING、DAVID数据库分别进行蛋白互作网络(protein-protein interactions,PPI)、基因本体(gene ontology,GO)富集分析和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析。[结果] 脾虚湿盛型核心中药为白术、甘草、茯苓、党参,脾肾阳虚型核心中药为补骨脂、吴茱萸、肉豆蔻。两证型核心中药的有效成分主要为3β-乙酰氧基苍术酮、槲皮素、常春藤皂苷元、木犀草素、二十四烷酸、β-谷甾醇。关键靶点为白介素-6(interleukin-6,IL-6)、细胞肿瘤抗原p53(tumor protein p53,TP53)、肿瘤坏死因子(tumor necrosis factor,TNF)、血管内皮生长因子A(vascular endothelial growth factor A,VEGFA)、白介素-1B(interleukin-1B,IL-1B)。GO和KEGG富集分析显示中药治疗IBS-D与基因表达、转录调控、信号转导、免疫反应、炎症反应等多种途径相关,并通过多种疾病通路、信号通路发挥治疗作用。白术、甘草、茯苓、党参四药可通过γ-氨基丁酸信号通路、G蛋白偶联乙酰胆碱受体信号通路参与治疗,补骨脂、吴茱萸、肉豆蔻在治疗中还与醛固酮调节的钠重吸收、胰岛素分泌等通路有关。[结论] 中药治疗脾虚湿盛型IBS-D以补气健脾为主,治疗脾肾阳虚型以温肾暖脾为主,两者作用机制皆存在“多成分、多靶点、多通路”的特点,并有部分重合,而两者的差异性则与证型内在病机有关。
英文摘要:
      [Objective] To explore the relationship between prescriptions and syndromes in irritable bowel syndrome with predominant diarrhea(IBS-D), based on data mining and network pharmacology. [Methods] All relevant literatures about spleen deficiency and dampness type and spleen and kidney Yang deficiency type IBS-D from the establishment date of the database to December 2020 in the literature database were collected, including China National Knowledge Infrastructure(CNKI), Chinese Biomedical Literature Service system(SinoMed), Wanfang Database and VIP Database for Chinese Technical Periodicals. After extracting the relevant prescription information, WPS Office Excel and IBM SPSS Modeler 18.1 software were used to conduct frequency analysis, analysis and association rule analysis, get the core Chinese medicine compatibility. Through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), the Encyclopedia of Traditional Chinese Medicine(ETCM), and the UniProt database to obtain the core active ingredients and targets of Chinese medicine, and obtain disease targets through the Gene-Disease Association Database(DisGeNET),Human Gene Comprehensive Database(GeneCarde), and Online Mendelian Inheritance in Man(OMIM) dalabase. The Chinese medicine targets and disease targets were subjected to itersection analysis, and the obtained results were imported into STRING and DAVID databases for protein-protein itretions(PP), gene ontology(G0) enrichment analysis, and Kyolo Encyelopedia of Genes aund Genomes (KEGG) pathway enichment analysis. Resulta] The core Chinese medicine for spleen deficiency and dampness type were Atraetylodis macrocephalae thizoma, Glyeytrhisae uralensis Fisch, Poria cocos and Codonopsis radix, and the core Chinese medicine for spleen and kidney Yang deficieney type were Psoralea eorylifolia, Eoodive Fructus and Mristicowe semen. The core components were 3β- acetoxya-tractylone,quercetin, hederagenin, luteolin, lgnoceric acid, β -itoterol. Key targets were interleukin 6 (IL- 6), tumor protein p53 (TP53), tumor necrosis factor (TNF), vascular endothelial growth factor A (VEGFA), intereukin-1B(L-1B). G0 and KEGG enrichment analysis showed that traditional Chinese medicine treatment of IBS-D was associated with gene expression, transcriptional regulation,signal transduction, immune response, inflammiatory response and other pathways, and played a therapeutie role through a variely of disease pathways and signaling pathways. In addition, Aractylodis macrocephaloe thizoma, Glyeyhisae uralensis Fisch, Poria coeos and Codonopsis radix can participate in the treatment through the γ -aminobutyriec acid signaling pathway and the G protein -coupled acetylecholine reeptor signaling pathway. Psoradleae fructus, Evodiae fructus and Myristicae semen were also involved in the treatment of aldosterone- regulated sodium reabsorption, insulin scretion and other pathwaye. [Conclusion] Traditional Chinese medicine in the treal-ment of IBS-D with spleen deficiency and dampness mainly focuses on tonifying Qi and strengthening the spleen, while the spleen and kidney Yang deficieney mainly warms the kidney and the epleen. And gome overlap, and the diference between the two is related to the interal puthogeneais of the syndrome.
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