网络药理学结合体内实验研究藿香-龙胆草药对治疗鼻窦炎的机制  

Mechanism of Huoxiang(Agastache Rugosus)-Longdancao(Gentian)in the Treatment of Sinusitis by Network Pharmacology Technology Combined with in Vivo Experiment

作　　者：蔺婷[1] 熊静 兰超 田道法[1,2] 吴婷 周振峰 LIN Ting;XIONG Jing;LAN Chao;TIAN Daofa;WU Ting;ZHOU Zhenfeng(Hunan Provincial Key Laboratory for the Prevention and Treatment of Ophthalmology and Otolaryngology Diseases with Traditional Chinese Medicine,Hunan Provincial Ophthalmology and Otolaryngology Diseases Prevention and Treatment with Traditional Chinese Medicine and Visual Function Protection Engineering and Technological Research Center,Hunan University of Chinese Medicine,Changsha Hunan 410208,China;Yueyang Hospital of Chinese Medicine,Yueyang Hunan 414000,China)

机构地区：[1]湖南中医药大学中医药防治眼耳鼻咽喉疾病湖南省重点实验室,湖南中医药大学湖南省中医药防治眼耳鼻喉疾病与视功能保护工程技术研究中心,湖南长沙410208 [2]岳阳市中医医院,湖南岳阳414000

出　　处：《中医药导报》2023年第11期42-49,共8页Guiding Journal of Traditional Chinese Medicine and Pharmacy

基　　金：湖南省自然科学基金项目(2021JJ70052);湖南省中医药管理局基金项目(2021070)。

摘　　要：目的:通过网络药理学和体内实验研究藿香-龙胆草治疗鼻窦炎的作用机制。方法:通过TCMSP、Swiss Target Prediction数据库筛选藿香-龙胆草有效活性成分和作用靶点;经GeneCards、OMIM、Durgback平台获取“鼻窦炎”疾病靶点后与药物作用靶点取交集;利用String、Cytoscape3.8.2软件构建中药成分-靶点网络和蛋白互作网络图(PPI),并进行基因本体论(GO)和京都基因和基因组百科全书(KEGG)信号通路富集分析。建立鼻窦炎大鼠模型,采用ELISA法检测TNF-α、IL-1β、IL-17、IL-6水平;Western blotting法检测TNF-α、IL-1β、IL-6、NF-κB p65和IL-17C蛋白相对表达量。结果:筛选得到藿香-龙胆草有效活性成分10个,药物作用靶点163个,药物成分与疾病交集靶点110个;藿香-龙胆草药对的核心活性成分为槲皮素、龙胆碱、龙胆苦苷;核心靶点为AKT1、TP53、IL-6、VEGEA、TNF;KEGG富集主要涉及的通路有脂质与动脉粥样硬化通路、IL-17信号通路、TNF信号通路等。ELISA结果显示:与对照组比较,模型组大鼠血清TNF-α、IL-1β、IL-6、IL-17水平均明显升高(P<0.01);与模型组比较,藿香-龙胆草组和阳性药组大鼠血清TNF-α、IL-1β、IL-6、IL-17水平均明显降低(P<0.05或P<0.01);与阳性药组比较,藿香-龙胆草组大鼠血清TNF-α、IL-1β、IL-6、IL-17水平升高,差异有统计学意义(P<0.05)。Western blotting结果显示:与对照组比较,模型组大鼠鼻黏膜组织中TNF-α、IL-1β、NF-κB p65、IL-6、IL-17C蛋白相对表达量均明显升高(P<0.01);与模型组比较,藿香-龙胆草组和阳性药组大鼠TNF-α、IL-1β、IL-6、IL-17C蛋白相对表达量均明显降低(P<0.01);与阳性药组比较,藿香-龙胆草组大鼠TNF-α、IL-1β、IL-6、IL-17C蛋白相对表达量明显升高,NF-κB p65蛋白相对表达量明显降低,差异均有统计学意义(P<0.01)。结论:藿香-龙胆草能通过IL-17激活NF-κB通路抑制炎症因子TNF-α、IL-1β和IL-6的表达起到治疗Objective:To investigate the mechanism of Huoxiang(Agastache rugosus)-Longdancao(Gentian)in the treatment of sinusitis by network pharmacology technology and in vivo experiment.Methods:TCMSP and Swiss Target Prediction database were used to screen the active ingredients and targets of Huoxiang(Agastache rugosus)-Longdancao(Gentian).The disease targets of"sinusitis"were obtained by GeneCards,OMIM and Durgback platforms and then intersected with drug targets.The traditional Chinese medicine component-target network and protein interaction network(PPI)were constructed by String and Cytoscape 3.8.2 software.And Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)signal pathway enrichment analysis were performed.Rat model of sinusitis was established.The levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-17(IL-17)and interleukin-6(IL-6)were detected by ELISA.The protein expressions of TNF-α,IL-1β,IL-6,NF-κB p65 and IL-17C were detected by Western blotting.Results:A total of 10 active ingredients,163 drug targets,and 110 intersection targets of drug components and diseases were screened.The core active ingredients of Huoxiang(Agastache rugosus)-Longdancao(Gentian)were quercetin,gentioline and gentiopicrin.The core targets were AKT1,TP53,IL-6,VEGEA and TNF.KEGG enrichment was mainly involved in lipid and atherosclerosis pathway,IL-17 signaling pathway,TNF signaling pathway,etc.The results of ELISA showed that compared with the control group,the serum levels of TNF-α,IL-1β,IL-6 and IL-17 increased significantly in model group(P<0.01).Compared with the model group,the serum levels of TNF-α,IL-1β,IL-6 and IL-17 decreased significantly in the agastache-gentian group and positive drug group(P<0.05 or P<0.01).Compared with the positive drug group,the serum levels of TNF-α,IL-1β,IL-6 and IL-17 increased in the agastagus-gentian group(P<0.05).Western blotting results showed that compared with the control group,the protein relative expressions of TNF-α,IL-1β,NF-κB p65,IL-6 an

关 键 词：鼻窦炎 藿香 龙胆草 IL-17/NF-κB 网络药理学 大鼠 

分 类 号：R285.5[医药卫生—中药学]