[关键词]
[摘要]
目的 挖掘中医药治疗糖尿病牙周炎 (diabetic periodontitis,DP) 的组方规律,并探讨核心药物组合的作用机制。方法 以中国知网、万方数据库、维普中文期刊、中国生物医学文献服务系统收录的中医药治疗 DP文献为资料来源,建立 DP 处方信息数据库,运用 Excel 2021、SPSS Modeler 18.0 和 SPSS Statistics 26.0,对纳入中药进行频次、功效分类、性味归经统计,并进行关联规则分析和聚类分析,筛选出核心药物组合;通过中药系统药理学数据库与分析平台 (TCMSP) 、HERB 获取核心药物组合的活性成分,预测药物作用靶点;运用GeneCards 预测疾病相关靶点;运用 Venny 平台得到疾病与药物的交集靶点;运用 Cytoscape 建立“活性成分-靶点”网络,筛选出关键成分;以 STRING 平台数据为基础,利用 Cytoscape 软件构建蛋白质-蛋白质相互作用网络,筛选核心靶点;通过 DAVID 数据库对交集靶点进行基因本体论 (GO) 和京都基因与基因组百科全书(KEGG) 富集分析;采用 AutoDockVina 对关键成分与核心靶点进行分子对接。结果 共纳入中医药治疗 DP 文献 36 篇,提取方剂 50 首,涉及药物 100 味;最常见的药物有泽泻、熟地黄、黄芪等,使用最多的药物类别为补虚药,药性以寒、温为主,药味以甘、苦味为主,归经以肾、肝经居多,系统聚类分析可归为 6 大类;筛选出牡丹皮-山茱萸-熟地黄为核心药物组合,涉及 18 个活性成分、164 个作用靶点,与 DP 有 104 个交集靶点;槲皮素、豆甾醇、山奈酚、β-谷甾醇、四氢鸭脚木碱、谷甾醇等为核心成分,AKT1、IL-6、TNF、IL-1B、PTGS2、JUN、TP53、ESR1、MMP9 等为关键靶点;GO 分析得到生物过程 3 724 项、细胞组成 228 项、分子功能 404 项;KEGG 分析显示主要涉及 235 条信号通路;分子对接显示关键靶点与核心成分具有良好亲和力。结论 DP 的中医治法主要以补虚为主,兼以清热利湿、活血化瘀、益气养阴,核心药物组合牡丹皮-山茱萸-熟地黄可通过多成分、多靶点、多通路治疗 DP,为临床诊疗提供参考。
[Key word]
[Abstract]
Objective To explore the prescription rules of traditional Chinese medicine (TCM) in the treatment of diabetes periodontitis (DP) and the acting mechanisms of core drug combination. Methods Based on the relevant literature retrieved from the CNKI,Wanfang,VIP and Sinomed,a DP prescription database was established. Excel 2021,SPSS Modeler 18.0 and SPSS Statistics 26.0 were used to conduct the statistics of the frequency,efficacy classifications, properties, flavors, and meridian tropism of the included drugs. Association rule analysis and cluster analysis were performed to screen out the core drug combinations. The active components and action targets of core drug combinations were obtained through TCMSP and HERB. The DP related disease targets were predicted using GeneCards. The Venny platform was used to obtain the intersection of disease targets and drug targets. Key components were screened by Cytoscape to establish an “active component-target” network. Based on STRING platform data,PPI network was constructed by Cytoscape to screen core targets. GO functional annotation and KEGG signaling pathway enrichment analysis were carried out for the intersection targets by DAVID. AutoDockVina was applied for molecular docking between core targets and key components. Results A total of 36 articles were included,and 50 prescriptions involving 100 Chinese herbal medicines were extracted. Alismatis Rhizoma,Rehmanniae Radix Praeparata and Astragali Radix were the most common drugs. The most used drug category was deficiency-nourishing drugs. The properties of the herbs were mainly cold and warm,the major flavors were sweet and bitter,and the main meridian tropisms were kidney and liver. Six categories were classified by clustering analysis. Moutan Cortes- Corni Fructus- Rehmanniae Radix Praeparata was screened out as the core drug combination involving 18 active components,164 drug action targets and 104 intersection of DP targets and drug combination targets. Quercetin,stigmasterol,kaempferol,β-sitosterol,tetrahydroalstonine,and sitosterol were the key components,and AKT1,IL-6,TNF,IL-1B,PTGS2,JUN,TP53,ESR1,and MMP9 were the core targets. GO analysis revealed 3 724 biological processes,228 cellular components and 404 molecular functions. KEGG analysis showed that DP was treated by the core drug combination through regulating 235 signaling pathways. Molecular docking results showed that there was a good affinity between the core target and the key component. Conclusion Tonifying deficiency is the main treatment methods of TCM for DP, accompanied by clearing heat and removing dampness, activating blood circulation and removing blood stasis,replenishing qi and nourishing yin. Core drug combination (Moutan Cortes- Corni Fructus- Rehmanniae Radix Praeparata) treats DP through multi-component, multi-target and multi-pathway,which provide a reference for clinical diagnosis and treatment.
[中图分类号]
R285.6;R285.5
[基金项目]
国家自然科学基金项目 (81973684);四川省自然科学基金项目(23NSFSC2574);成都中医药大学杏林学者青年进阶人才专项(QJJJ2023005)。