摘要
目的基于数据库数据分析口干症证型,筛选出口干症的高频中药药对并分析其作用机制。方法以“口干、口腔干燥症、口腔干燥综合征、燥痹”为主题词,检索中国知网、万方、维普数据库,检索时限为1980年10月—2022年9月。经文献筛选、资料提取后,使用Excel软件对疾病种类、证型、证素及高频药物的使用频数、四气、五味、归经和功效分类进行统计,使用SPSS软件对374味药物进行关联分析,对使用频次大于50的40味高频药进行聚类分析、因子分析以挖掘出治疗口干症的高频中药药对。从PubChem、TCMSP数据库获取支持度、实例数最高的高频中药药对的主要活性成分及靶点,在GeneCards、DrugBank数据库中检索口干症的疾病靶点。取交集靶点,导入Cytoscape3.8.0软件进行PPI绘制,上传至DAVID进行生物学功能分析(GO分析、KEGG分析)。结果口干症在干燥综合征、糖尿病、中老年增龄性口干等疾病中最常见;证型以阴虚内热、肺胃阴虚、气阴两虚为主;病位证素多集中在肺、胃;病性证素以阴虚、热、气虚最常见。治疗口干症的药物中,麦冬出现频次最高;高频药中四气五味以寒、温、甘、苦为主;多入肺、胃经,功效分类以补虚药多见。根据关联分析得出支持度、实例数最高的高频中药药对是“麦冬—玉竹”,依据聚类分析和因子分析得出三类新方。麦冬、玉竹高频药对有效化学成分15种,共得到446个潜在作用靶点。高频中药药对与口干症的共同作用靶点有STAT3、MAPK3、MAPK1、ESR1、EGFR、IL2等。GO富集分析结果显示,高频中药药对—疾病交集靶点具有生物学过程(BP)258条、细胞成分(CC)34条、分子功能(MF)64条,BP主要涉及细胞内信息传递、蛋白质磷酸化、细胞凋亡过程的正向调节等;CC主要涉及小腔、大分子复合物、黏着斑等;MF主要涉及蛋白质磷酸酶结合等。高频中药药对—疾病交集靶点共富集于癌症通路、PI3K-Akt信号通路、甲状腺激素信号通路、内分泌抵抗通路、JAK-STAT信号通路等128条通路中。结论口干症可能以肺、脾、胃等脏腑阴虚、气虚为始动因素,津液不能润泽口腔为其根本病机,兼热、湿、瘀等证象。“麦冬—玉竹”为治疗口干症的高频中药药对,主要通过AKT1、ESR1、EGFR等靶点,调控PI3K-Akt、JAK-STAT等信号通路发挥作用。
Objective To investigate the fundamental pathogenesis,to screen out the high-frequency TCM drug pairs,and to analyze their mechanism of action of xerostomia.Methods With"dry mouth,xerostomia,Sjogren's syn⁃drome,dry mouth"as the theme heading,CNKI,Wanfang and Weipu databases were searched,and the search period was from October 1980 to September 2022.After literature screening and data extraction,Excel software was used to col⁃lect statistics on the use of disease types,syndromes,syndrome elements and frequency of high-frequency drugs,four qi,five flavors,attribution and efficacy classification,and correlation analysis was conducted on 374 flavor drugs by SPSS soft⁃ware;40 flavor high-frequency drugs with a frequency greater than 50 were clustered,and factor analysis was used to dig out the core drug pairs for the treatment of xerostomia.The main active ingredients and targets of core drug pairs with the highest degree of support and the highest number of examples were obtained from PubChem and TCMSP databases,and the disease targets of xerostomia were searched in GeneCards and DrugBank databases.The intersection targets were taken and imported into Cytoscape 3.8.0 software for PPI network mapping,and were uploaded to DAVID for biological function analysis(GO analysis,KEGG analysis).Results Xerostomia was the most common in Sjogren's syndrome,diabetes,and elderly aged dry mouth.The symptom types were mainly yin deficiency and internal heat,lung and stomach yin defi⁃ciency,and qi and yin deficiency.Disease evidence was mostly concentrated in the lungs and stomach;as for pathogenic factors,yin deficiency,heat,and qi deficiency were the most common syndromes.Among the drugs used to treat xerosto⁃mia,Maidong had the highest frequency of 296 times.Cold,warm,sweetness and bitterness were the main four qi and five flavors in high-frequency medicine.They entered the lungs and stomach meridians mainly,and tonifying deficiency drug was the mainly efficacy classification.According to the correlation analysis,the core drug pairs with the highest de⁃gree of support and the highest number of instances was"Maidong-Yuzhu",and three types of new formulas were obtained according to cluster analysis and factor analysis.Maidong and Yuzhu high-frequency drug pair had 15 active chemical com⁃ponents,and 446 potential targets were obtained.The common targets of high-frequency drug pair and xerostomia were STAT3,MAPK3,MAPK1,ESR1,EGFR,and IL2,etc.GO enrichment analysis showed that the core drug pair-disease intersection targets had 258 biological processes(BP),34 cellular components(CC),and 64 molecular functions(MF),and BP mainly involved intracellular information transmission,protein phosphorylation,and positive regulation of apopto⁃sis.CC mainly involved small cavities,macromolecular complexes,and adhesion spots,etc.;MF mainly involved protein phosphatase binding,etc.The core drug pair-disease intersection targets were enriched in 128 pathways,including cancer pathway,PI3K-Akt signaling pathway,thyroid hormone signaling pathway,endocrine resistance pathway,and JAK-STAT signaling pathway,etc.Conclusions Xerostomia may be caused by deficiency of yin and qi in the lungs,spleen,stom⁃ach and other organs,and the inability of jin fluid to moisturize the mouth is the fundamental pathogenesis,as well as heat,moisture,stasis and other symptoms."Maidong-Yuzhu"is the core high-frequency drug pair,which mainly regu⁃lates the signaling pathways such as PI3K-Akt and JAK-STAT through targets such as AKT1,ESR1,and EGFR.
作者
于诗雨
李翠娟
孙理军
巩振东
胡勇
YU Shiyu;LI Cuijuan;SUN Lijun;GONG Zhendong;HU Yong(School of Basic Medicine,Shaanxi University of Chinese Medicine,Xianyang 712046,China;不详)
出处
《山东医药》
CAS
2023年第15期49-54,共6页
Shandong Medical Journal
基金
国家自然科学基金项目(81202614)
陕西省自然科学基础研究计划项目(2021JM-475,2023-JC-YB-675)
陕西省教育厅重点科研计划项目(18JS030,SMZX202102)
咸阳市中医体质与疾病防治重点实验室重点研发计划项目(2019K01-53)。
