目的 基于数据挖掘和网络药理学，探究内服中药治疗痔疮的用药规律及关键中药的作用机制，为痔疮的临床治疗和研究提供参考。方法 检索相关数据库、书籍中的有关方剂，建立中药治疗痔疮数据库。通过Microsoft Office Excel 2017统计中药的性味、归经，利用Cytoscape 3.7.2软件筛选主要中药。利用IBM SPSS Modeler 18.0软件分析主要中药关联规则；利用IBM SPSS Statistics 23.0软件进行主成分分析。运用TCMSP、Uniprot、Genecards、DAVID等数据库分析关键中药治疗痔疮的网络药理学机制。结果 纳入319首痔疮方剂涉及中药257味，累计使用2232次。这些内服中药多为清热药、补虚药、止血药，且以性寒、味苦，入肝经或大肠经为主。拓扑学筛选得到当归、枳壳、槐米、槐角、黄芩等34味主要中药，由其组成的二联、三联组合的关联程度高；主成分分析提取13个公因子。网络药理学研究显示，关键中药组合槐米-枳壳-地榆的主要药效成分有槲皮素、山柰酚、川陈皮素、β-谷甾醇等，涉及白细胞介素-6（interleukin-6，IL-6）、肿瘤坏死因子（tumor necrosis factor，TNF）、基质金属蛋白酶（matrix metalloproteinase-9，MMP9）、肿瘤蛋白P53（cellular tumor antigen p53，TP53）、趋化因子8（interleukin-8，CXCL8）等关键靶点。基因本体（gene ontology，GO）富集涉及细胞增殖、凋亡过程调控、细胞因子活性、酶（蛋白）结合等主要生物学类型。京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）主要富集在TNF信号通路、炎性肠病、磷脂酰肌醇-3-羟激酶（phosphatidylinositol-3-hydroxykinase，PI3K）-蛋白激酶B（protein kinase B，Akt）信号通路等。结论 中药内服治疗痔疮应以清热药、补虚药、止血药为主，槐米-枳壳-地榆为关键中药组合。其治疗作用可能是通过影响IL-6、TNF、MMP9等关键靶点，调控TNF信号通路、炎性肠病、PI3K-Akt信号通路等实现。

Objective Based on data mining and network pharmacology, to explore the medication rules of oral traditional Chinese medicine for hemorrhoids and the mechanism of key traditional Chinese medicine, which is expected to provide references for the clinical treatment and research of hemorrhoids. Methods The related databases and books about hemorrhoids prescriptions were screened, and a database for treating hemorrhoids with traditional Chinese medicine was established. Microsoft Office Excel 2017 was used to calculate the nature, flavor and meridian of traditional Chinese medicine. The cytoscape 3.7.2 software was applied to select core traditional Chinese medicine. Then making use of IBM SPSS Modeler 18.0 software to analyze core traditional Chinese medicine association rules; IBM SPSS Statistics 23.0 software was used to perform core traditional Chinese medicine principal component analysis. TCMSP, Uniprot, Genecards, DAVID and other databases are utilized to conduct network pharmacological analysis of the mechanism of key traditional Chinese medicine in the treatment of hemorrhoids. Results A total of 319 research formulas were included, involving 257 traditional Chinese medicine, which were used 2232 times in total. The traditional Chinese medicine for treating hemorrhoids were mostly heat-clearing medicines, tonic medicines, and hemostatic medicines; At the same time, these traditional Chinese medicine were mainly based on cold in nature and bitter taste into the liver meridian or large intestine meridian. After topological screening, 34 main traditional Chinese medicine including Angelicae Sinensis Radix, Aurantii Fructus, Sophorae Flos, Sophorae Fructus, Scutellariae Radix were obtained. And the double and triple combinations of them had a high degree of correlation. And 13 common factors were extracted in principal component analysis. The results of network pharmacology study implied that the key composition Sophorae Flos-Aurantii Fructus-Sanguisorbae Radix treating hemorrhoids mainly involved interleukin-6 (IL-6), tumor necrosis factor (TNF), matrix metalloproteinase-9 (MMP9), cellular tumor antigen p53 (TP53), interleukin-8 (CXCL8) and other important targets; And the main active compounds were quercetin, kaempferol, nobiletin, β-sitosterol and so on. Gene ontology (GO) enrichment mainly involved biological types such as cell proliferation, regulation of apoptosis, cytokine activity, and enzyme (protein) binding. While Kyoto encyclopedia of genes and genomes (KEGG) enrichment mainly involved TNF signaling pathway, inflammatory bowel disease, PI3K-Akt signaling pathway and so on. ConclusionsThe treatment of hemorrhoids with traditional Chinese medicine should be based on heat-clearing medicine, tonic medicine and hemostatic medicine; Sophorae Flos-Aurantii Fructus-Sanguisorbae Radix were the key traditional Chinese medicine combinations in the treatment of hemorrhoids. The therapeutic effect may be achieved by affecting key targets such as IL-6, TNF, MMP9, and regulating TNF signaling pathways, inflammatory bowel disease, PI3K-Akt signaling pathways.

R283.21

国家自然科学基金项目（81960748）