白头翁汤治疗溃疡性结肠炎分子机制的网络药理学分析及初步验证  

Network pharmacological analysis and preliminary validation of mechanisms of Baitouweng Decoction in treatment of ulcerative colitis

作　　者：缪志伟[1] 徐艳[1] 宁丽琴[2] 严晶[3] 顾鸣佳[3] 叶柏[2] MIAO Zhi-wei;XU Yan;NING Li-qin;YAN Jing;GU Ming-jia;YE Bai(Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine,Zhangjiagang 215600,China;Jiangsu Province Hospital of Chinese Medicine,Nanjing 210029,China;Nanjing University of Chinese Medicine,Nanjing 210023,China)

机构地区：[1]南京中医药大学附属张家港医院,江苏张家港215600 [2]江苏省中医院,江苏南京210029 [3]南京中医药大学,江苏南京210023

出　　处：《中国中药杂志》2020年第8期1808-1815,共8页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(81503536);江苏省自然科学基金青年基金项目(BK20191092);苏州市科技发展计划项目(SYSD2017007);张家港市科技支撑计划项目(ZKS1839)。

摘　　要：该文通过网络药理学分析白头翁汤治疗溃疡性结肠炎(UC)的分子机制,并通过动物实验对相关靶点作初步验证。应用Cytoscape软件,通过TCMSP,GeneCards,Uniprot数据库构建"活性成分-靶点-疾病"网络。通过STRING数据库构建蛋白互作网络,推测核心靶点。使用R软件对靶点进行GO,KEGG富集分析。使用Autodock Vina软件对活性成分和核心靶点进行分子对接。用白头翁汤干预葡聚糖硫酸钠(DSS)诱导UC小鼠,通过HE染色法观察小鼠结肠的病理改变,通过免疫组化分析相关基因的表达情况。结果表明,通过网络药理学从白头翁汤中找到26个有效成分,30个核心靶点。GO富集分析显示,这些基因主要影响核受体的活性、转录因子的活性、类固醇激素受体活性、泛素样蛋白连接酶结合、蛋白质异二聚化活性、转录辅助因子的结合等生物过程。KEGG富集分析显示,P53信号通路、EGFR信号通路、TNF信号通路、PI3K-AKT信号通路和一些癌症相关通路基因富集较多。分子对接显示,与有效成分对接较好的基因有EGFR,PPARG,CASP3,NOS3,caspase-9,CCND1,ADH,IL6,NFKB1。实验验证白头翁汤对小鼠结肠病理有改善作用,EGFR是其作用的靶点之一。该研究证明白头翁汤可通过多靶点、多通路治疗UC,为未来研究提供了理论依据。The aim of this paper was to explore the pharmacological mechanism of Baitouweng Decoction in the treatment of ulcerative colitis(UC) by network pharmacology and to preliminarily verify the related targets by animal experiments. Cytoscape software was used to construct "ingredient-target-disease" network through TCMSP, GeneCards and Uniprot databases. The protein interaction network was constructed using STRING database, and the core targets were speculated. The GO and KEGG enrichment analysis was conducted using R software. Autodock Vina software was used for molecular docking of ingredients and core targets. UC mice induced by dextran sodium sulfate(DSS) were treated by Baitouweng Decoction. The pathological changes of colon tissues were observed by HE staining, and the expression levels of related genes were analyzed by immunohistochemistry.The results showed that 26 active ingre-dients and 30 core targets were found in Baitouweng Decoction through network pharmacology. GO enrichment analysis showed that these genes mainly affected nuclear receptor activity, transcription factor activity, steroid hormone receptor activity, ubiquitin-like protein ligase binding, protein heterodimerization activity, transcription cofactor binding and other biological processes. KEGG enrichment analysis showed that P53 signaling pathway, EGFR signaling pathway, TNF signaling pathway, PI3 K-AKT signaling pathway and some cancer-related pathways were enriched. Molecular docking showed that EGFR, PPARG, CASP3, NOS3, caspase-9, CCND1, ADH, IL6 and NFKB1 were better docked with active ingredients. The experiments verified that Baitouweng Decoction could improve the colon pathology of mice, and EGFR is one of the related targets. Our study suggested that Baitouweng Decoction could treat UC through multiple targets and pathways, which provided a theoretical basis for future research.

关 键 词：白头翁汤 溃疡性结肠炎 网络药理学 分子对接 

分 类 号：R285[医药卫生—中药学]