基于网络药理学与实验验证探讨射干止咳胶囊治疗感染后咳嗽的作用机制  

Based on network-based pharmacology and experimental validation to explore the mechanism of Shegan Zhike capsule in the treatment of post infectious cough

作　　者：任铭 董笑博 齐越 尹江涛 鞠俭奎[2] 甘雨[2] 张颖[2] REN Ming;DONG Xiaobo;QI Yue;YIN Jiangtao;JU Jiankui;GAN Yu;ZHANG Ying(School of Pharmacy,Liaoning University of Traditional Chinese Medicine,Shenyang 110032,China;The Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110034,China)

机构地区：[1]辽宁中医药大学药学院,辽宁沈阳110032 [2]辽宁中医药大学附属第二医院,辽宁沈阳110034

出　　处：《沈阳药科大学学报》2025年第3期274-282,共9页Journal of Shenyang Pharmaceutical University

基　　金：国家“重大新药创制”科技重大专项资助项目(2017ZX09301-019);沈阳市科技局中青年科技创新人才项目(RC210047);辽宁省教育厅项目(LJKZ0904);辽宁省科技厅博士启动(2022-BS-068)。

摘　　要：目的采用网络药理学和动物实验探讨射干止咳胶囊治疗感染后咳嗽的分子机制。方法通过中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)获得射干的活性成分,利用Swiss Target Prediction获取射干的相关靶点,并于GeneCards、OMIM、DisGeNET数据库筛选出的疾病靶点取交集获得射干止咳胶囊治疗感染后咳嗽的潜在靶点;采用STRING和Cytoscape 3.9.0构建“药物-有效成分-交集靶点”网络并筛选关键靶点;然后进行基因本体(Gene Ontology,GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)信号通路富集分析;Western blot法检测肺组织叉头状转录因子3(forkhead box protein,Foxp3)、维甲酸相关孤儿核受体γt(retinoic-acid-related orphan nuclear receptor gamma t,RORγt)蛋白表达。结果经过筛选,射干止咳胶囊中的木犀草素、野鸢尾黄素、异鼠李素、鸢尾甲黄素A、鸢尾甲黄素B、鸢尾黄素等多个关键活性成分,可能通过作用在蛋白质激酶Bα(protein kinase Bα,AKT1)、肿瘤坏死因子(tumor necrosis factor,TNF)、白细胞介素-6(interleukin-6,IL-6)、血管内皮生长因子A(vascular endothelial growth factor A,VEGFA)等核心基因表达的蛋白上参与感染后咳嗽的治疗;KEGG富集分析所涉及的通路包括FoxO信号通路(FoxO signaling pathway)、IL-17信号通路(IL-17 signaling pathway)、Th17细胞分化(Th17 cell differentiation)、Th1和Th2细胞分化(Th1 and Th2 cell differentiation)、B细胞受体信号通路等;动物实验验证射干止咳胶囊可影响Foxp3、RORγt蛋白表达。结论射干止咳胶囊可以影响Foxp3、RORγt蛋白表达,调控Treg/Th17平衡通路发挥其抗炎作用,有效治疗感染后咳嗽。Objective Network pharmacology and animal studies were used to explore the molecular mechanism of the treatment of post-infectious cough by Shegan Zhike capsule.Methods The active ingredients of the Shegan Zhike capsule were obtained from TCMSP,the relevant targets of the Shegan Zhike capsule were obtained by Swiss Target Prediction,and the potential targets of Shegan Zhike capsule for the treatment of post-infectious cough were obtained by intersecting the disease targets screened by GeneCards,OMIM and DisGeNET databases;STRING and Cytoscape 3.9.0 were used to construct the"Drug-Active ingredient-Intersecting target"network and screen the key targets;then,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)signalling pathway enrichment analyses were carried out;and the lung tissue was examined by Western blot.Foxp3 and RORγt were detected by Western blot.Results After screening,several key active ingredients such as iuteolin,irigenin,isorhamnetin,iristectorigenin A,iristectorigenin B,and tectorigenin in Shegan Zhike capsule may be involved in the treatment of post-infectious cough by acting on proteins expressed by core genes such as protein kinase Bα(AKT1),tumour necrosis factor(TNF),interleukin-6(IL-6),and vascular endothelial growth factor A(VEGFA);KEGG enrichment analysis involved pathways including lipid and atherosclerosis,interleukin-17 signalling pathway,T-cell receptor signalling pathway,Th17 cell differentiation,etc.Animal experiments verify that Shegan Zhike capsule can affect Foxp3 and RORγt protein expression.Conclusion Shegan Zhike capsule can affect Foxp3 and RORγt protein expressions,regulation of Treg/Th17 balance pathway to play its anti-inflammatory effect,effective treatment of post-infectious cough.

关 键 词：射干 感染后咳嗽 网络药理 作用机制 药理实验 

分 类 号：R285[医药卫生—中药学]