芍倍注射液“异病同治”直肠脱垂和混合痔的网络药理学作用机制研究

An exploration on mechanisms of treatment of different diseases with the same therapeutic method of the Shao-bei injection in treating rectal prolapse and mixed hemorrhoids based on network pharmacology

目的:通过网络药理学方法探究芍倍注射液“异病同治”直肠脱垂和混合痔的共同作用机制。方法:采用中药系统药理学数据库与分析平台(TCMSP)检索芍倍注射液的活性成分对应的作用靶点,并通过Uniprot数据库对基因进行标准化处理。利用GeneCards和OMIM数据库检索直肠脱垂和混合痔相关疾病靶点。利用Cytoscape 3.7.1软件构建“药物-成分-靶点-疾病”网络图;运用STRING数据库构建蛋白质-蛋白质相互作用网络图,通过Cytoscape 3.7.1软件构建“药物-疾病”核心靶点网络图。利用DAVID在线数据库平台对芍倍注射液治疗直肠脱垂和混合痔的共同靶点进行基因本体论(GO)富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。结果:检索得到芍倍注射液活性成分作用靶点27个,直肠脱垂靶点884个,混合痔靶点140个,药物与疾病的共同靶点10个,涉及肿瘤抑制蛋白p53(Tumor Suppressor Protein p53,TP53)、白细胞介素-6(Interleukin 6,IL-6)、肿瘤坏死因子(Tumor Necrosis Factor,TNF)等。GO生物过程分析共得到55个生物过程、2个细胞组分、7个分子功能,涉及对抗生素的反应、凋亡过程的正调控、一氧化氮生物合成过程的正调控、蛋白激酶B信号转导的正调控、半胱氨酸型内肽酶活性等生物过程。KEGG通路富集分析得到26条信号通路,主要涉及TNF信号通路、癌症途径、血管内皮生长因子(Vascular Endothelial Growth Factor,VEGF)信号通路、p53信号通路、丝裂原活化蛋白激酶(Mitogen-Activated Protein Kinase,MAPK)信号通路等。结论:芍倍注射液“异病同治”直肠脱垂和混合痔具有多成分、多靶点、多通路的特点,为芍倍注射液在临床中治疗直肠脱垂和混合痔提供理论依据,但芍倍注射液治疗疾病的关键靶点和通路仍需要进一步的实验验证。

Objective:To explore the common mechanism of the Shao-bei injection(芍倍注射液)in treating rectal prolapse and mixed hemorrhoids by network pharmacology.Methods:All targets of the chemical components of the Shao-bei injection were obtained by searching for TCMSP,and the genes were standardized through Uniprot database.Related disease targets for rectal prolapse and mixed hemorrhoids are screened through GeneCards and OMIM databases.The network diagram of“drug-component-target-disease”was constructed by the software of Cytopscape 3.7.1,the PPI network diagram of protein interaction was constructed by STRING database,and the network diagram of“drug-disease”core target was constructed by the software of Cytopscape 3.7.1.The DAVID online database platform was used to analyze GO biological process and KEGG pathway enrichment of common targets of the Shao-bei injection in treating rectal prolapse and mixed hemorrhoids.Results:A total of 27 potential targets of the Shao-bei injection were screened,with 884 rectal prolapse targets,and 140 mixed hemorrhoids targets,and 10 common targets of drugs and diseases,involving TP53,IL-6,TNF,etc..The GO biological process analysis obtained 55 biological processes,and 2 cell components and 7 molecular functions,including the response to antibiotic,positive regulation of apoptotic process,positive regulation of nitric oxide biosynthetic process,positive regulation of protein kinase B signaling,cysteine-type endopeptidase activity and other biological processes.The enrichment analysis of KEGG pathway gained 26 signal pathways.It mainly involves TNF signaling pathway,cancer pathway,VEGF signaling pathway,p53 signaling pathway,MAPK signaling pathway,etc..Conclusions:The Shao-bei injection based on treatment of different diseases with the same therapeutic method on rectal prolapse and mixed hemorrhoids have the characteristics of multiple components,multiple targets and multiple pathways,which provides theoretical basis for the Shao-bei injection on rectal prolapse and mixed hemorrhoids,but the key targets and pathways of the Shao-bei injection on diseases still need further experimental verification.