基于网络药理学及“上病下取”理论探讨“苦杏仁-莱菔子”治疗儿童慢性咳嗽的作用机制  

Exploration of the mechanism of“Kuxingren-Laifuzi”in the treatment of chronic cough in children based on network pharmacology and the theory of“treating the disease in the upper part by managing the lower”

作　　者：杨柳岸 白晓红[2] 修禅 吕启慧 Yang Liu′an;Bai Xiaohong;Xiu Chan;Lv Qihui(Liaoning University of Traditional Chinese Medicine,Shenyang Liaoning 110847;The Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang Liaoning 110032)

机构地区：[1]辽宁中医药大学,辽宁沈阳110847 [2]辽宁中医药大学附属医院,辽宁沈阳110032

出　　处：《山西中医药大学学报》2023年第4期435-444,共10页Journal of Shanxi University of Chinese Medicine

基　　金：重大疾病治疗重点专科建设(国家中医优势专科);辽宁省科学技术计划项目任务合同书(20170540625)。

摘　　要：目的:采用网络药理学方法研究“苦杏仁-莱菔子”药对治疗儿童慢性咳嗽的作用机制。方法:借助TCMSP、DrugBank、PharmGKB、OMIM、GeneCard等数据库,寻找“苦杏仁-莱菔子”药对的有效成分、作用靶点以及儿童慢性咳嗽的疾病基因,对交集基因进行GO基因功能富集分析及KEGG通路富集分析,构建交集基因的复方调控网络,寻找交集基因中的蛋白互作关系,构建蛋白互作网络并进行过滤,从而得到PPI网络核心;最后通过临床医案,从临床角度分析该药对的治法、治则。结果:研究显示“苦杏仁-莱菔子”活性成分对应的靶点基因与儿童慢性咳嗽疾病基因的交集靶点共有70个,作用于疾病的主要成分有左旋千金藤啶碱(l-SPD)、豆甾醇(stigmasterol)、雌酮(estrone)、甘草查尔酮B(licochalcone B),乌药碱(machiline)等。PPI核心网络得到12个核心靶点、145条边,核心靶点分别为SLC6A4、HSP90AA1、ESR1、PTGS2、SLC6A3、CAT、MAOB、ACHE、MAPK14、PGR、DRD2、DRD1,除了作用于气管的炎性反应以及改善消化系统功能外,也可以调节情志。通过对核心靶点进行GO基因富集分析可得到涉及细胞组件(BP)依次与化学成分的反应、生物质量的调节、细胞对化学刺激的反应等过程相关;生物学过程(CC)与内膜系统、膜的固有成分、质膜部分等相关;分子功能(MF)与阳离子结合、分子换能器活性、催化活性等相关。进行KEGG通路富集分析可得到涉及神经活性配体-受体相互作用、癌症相关通路、代谢通路、多巴胺能突触、钙信号通路、cAMP信号通路、PI3K-Akt信号通路等。结论:“苦杏仁-莱菔子”药对可通过多靶点、多通路治疗儿童慢性咳嗽。Objective:To study the mechanism of“Kuxingren-Laifuzi”in the treatment of chronic cough in children through network pharmacology.Methods:With the help of TCMSP,DrugBank,PharmGKB,OMIM,GeneCard and other databases,the effective components and action targets of couplet medicines of“Kuxingren-Laifuzi”and the disease genes of children′s chronic cough were searched.The GO gene function enrichment analysis and KEGG pathway enrichment analysis were carried out on the intersection genes to construct the compound regulatory network of intersection genes.The protein-protein interaction(PPI)in intersection genes was searched and the protein-protein interaction(PPI)network was constructed and filtered to obtain the core of PPI network.Finally,from the clinical point of view,the therapeutic methods and principles of the couplet medicines were analyzed through clinical medical records.Results:The research showed that there were 70 intersection targets between the target genes corresponding to the active ingredients of“Kuxingren-Laifuzi”and the disease genes of chronic cough in children.The main ingredients that acted on the disease were I-SPD,stigmasterol,estrone,licochalcone B,machiline,etc.The PPI core network had 12 core targets and 145 edges.The core targets were SLC6A4,HSP90AA1,ESR1,PTGS2,SLC6A3,CAT,MAOB,ACHE,MAPK14,PGR,DRD2 and DRD1.In addition to acting on the inflammatory response of the trachea and improving the digestive system,these core targets may also regulate emotional factors.Through GO gene enrichment analysis of the core targets,it could be found that BP was successively related to the reaction of chemical components,the regulation of biological quality,and the reaction of cells to chemical stimuli;CC was related to the endomembrane system,the intrinsic components of the membrane,and the plasma membrane;MF was related to cation binding,molecular transducer activity,and catalytic activity,etc.KEGG pathway enrichment analysis showed the information about the neural active ligand-receptor interactio

关 键 词：慢性咳嗽 苦杏仁 莱菔子 上病下取 儿童 网络药理学 医案 

分 类 号：R285.6[医药卫生—中药学]