目的 基于现代信息技术，分析以黄连Coptidis Rhizoma为核心治疗溃疡性结肠炎（ulcerative colitis，UC）的用药特点及规律，并阐明含黄连核心药物组治疗UC的分子机制，为其实验验证及新型方剂的研发奠定基础。方法 运用Apriori关联规则分析用于治疗UC的含黄连方剂，设置同时满足支持度≥0.25，置信度≥0.9且提升度≥1的药对为含黄连核心药物组，利用TCMSP、HERB和TCMID数据库检索活性成分并收集相应靶点，在GeneCard和OMIM数据库中以“ulcerative colitis”为关键词检索疾病靶点，运用Cytoscape 3.7.1软件构建“中药-成分-潜在靶点”网络图，通过STRING11.0构建蛋白-蛋白相互作用（protein-protein interaction，PPI）网络，并利用“微生信在线”网站对潜在靶点进行京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）通路可视化，采用分子对接软件AUTODOCK 4对关键靶点和成分进行对接验证。结果 数据库筛选得到161首目标方剂，主要涉及72味药；关联规则分析结果提示黄连与木香、甘草、白术、茯苓、当归是具有强关联性的5组药对，这6味核心药物一共含有144种成分、潜在靶点165个，其中有83个靶点分布在骨髓和淋巴组织，关键靶点有31个，包括丝氨酸/苏氨酸激酶1（serine/threonine kinase 1，AKT1）、肿瘤蛋白P53（tumor protein P53，TP53）、丝裂原活化蛋白激酶1（mitogen-activated protein kinase 1，MAPK1）、白细胞介素-6（interleukin-6，IL-6）、MAPK8。KEGG分析结果显示磷脂酰肌醇3-激酶（phosphatidylinositol 3-kinase，PI3K）-蛋白激酶B（protein kinase B，Akt）、IL-17、晚期糖基化终产物及其受体（advanced glycation end products-receptor advanced glycation end products，AGE-RAGE）等通路与含黄连核心药物组治疗UC密切相关。分子对接结果显示受体蛋白与中药成分的对接活性好，作用较稳定且与原配体的结合能相近，其中β-谷甾醇与原癌基因JUN具有最低的结合能。结论 初步分析了含黄连方剂治疗UC的配伍规律，并且在分子水平揭示了含黄连核心药物组治疗UC的机制，为后续含黄连方剂治疗UC的开发提供了理论基础。

Objective Based on modern information technology, the characteristics and rules of Huanglian (Coptidis Rhizoma) as the core in the treatment of ulcerative colitis (UC) were analyzed, and the molecular mechanism of drug group containing Coptidis Rhizoma as the core in the treatment of UC was clarified, which laid a foundation for its experimental verification and the research and development of new formulae. Methods Apriori association rule was used to analyze the prescriptions containing Coptidis Rhizoma for the treatment of UC. The drug pair that satisfied support ≥ 0.25, confidence ≥ 0.9 and lift ≥ 1 as the core drug group containing Coptidis Rhizoma. The TCMSP, HERB and TCMID databases were used to retrieve components and collect the corresponding targets. Disease targets were searched in GeneCard and OMIM databases using the keyword "ulcerative colitis". Cytoscape 3.7.1 software was used to construct the "TCM-ingredient-potential target" network diagram, the protein-protein interaction (PPI) network was constructed through STRING 11.0. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were used to visualize potential targets in the "Wei Sheng Xin Online" website, and AUTODOCK 4 software was used for docking verification of key targets and components. Results A total of 161 target prescriptions were screened, mainly involving 72 medicines. The results of association rule analysis showed that Coptidis Rhizoma had strong correlation with Muxiang (Aucklandiae Radix), Gancao (Glycyrrhizae Radix et Rhizoma), Baizhu (Atractylodis Macrocephalae Rhizoma), Fuling (Poria) and Danggui (Angelicae Sinensis Radix). These six core medicines had 144 ingredients and 165 potential targets, of which 83 targets were distributed in bone marrow and lymphoid tissues. There were key 31 targets, which included serine/threonine kinase 1 (AKT1), tumor protein P53 (TP53), mitogen-activated protein kinase 1 (MAPK1), interleukin-6 (IL-6), and MAPK8. In KEGG analysis, phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt), IL-17, advanced glycation end products-receptor advanced glycation end products (AGE-RAGE), etc. were closely related to UC in core drug group containing Coptidis Rhizoma. The results of molecular docking showed that the receptor protein had a good docking activity with traditional Chinese medicine components, the effect was relatively stable, and the binding energy was similar to that of the original ligand. Among them, β-sitosterol had the lowest binding energy with JUN. Conclusion The study preliminarily analyzed the compatibility of prescriptions containing Coptidis Rhizomin the treatment of UC, revealed the mechanism of the core drug group containing Coptidis Rhizoma in the treatment of UC at the molecular level, and provided a theoretical basis for the subsequent development of prescriptions containing Coptidis Rhizoma in the treatment of UC.

R285.64

国家自然科学基金面上项目（81873023）