基于网络药理学和药效实验探究一粒金经鼻给药治疗偏头痛的机制  

Mechanism of Yilijin(一粒金)Against Migraine by Nasal Administration Based on Network Pharmacology and Experimental Validation

作　　者：赵仕博 赵永烈 邓硕秋 张平安 林婧婧 郭丛[2] 刘安[2] 刘晓谦[2] 易红 ZHAO Shibo;ZHAO Yonglie;DENG Shuoqiu;ZHANG Pingan;LIN Jingjing;GUO Cong;LIU An;LIU Xiaoqian;YI Hong(The Third Affiliated Hospital of Beijing University of Chinese Medicine,Beijing 100029,China;Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China)

机构地区：[1]北京中医药大学第三附属医院,北京100029 [2]中国中医科学院中药研究所,北京100700

出　　处：《中医药导报》2023年第10期30-35,73,共7页Guiding Journal of Traditional Chinese Medicine and Pharmacy

基　　金：北京市中医药科技发展资金项目(JJ-2020-36);国家重点研发计划中医药现代化研究专项(2019YFC1709702);国家自然科学基金项目(81873256)。

摘　　要：目的:通过网络药理学与实验验证探讨一粒金经鼻给药治疗偏头痛的潜在作用机制。方法:通过中医药系统药理学数据库与分析平台(TCMSP)筛选一粒金的活性化学成分及其治疗偏头痛的相关靶点;检索GeneCards数据库、OMIM数据库、UniProt数据库、TTD数据库,汇总、去重后得到偏头痛的靶点;采用交集法获得一粒金和偏头痛的相关靶点;利用STRING平台,构建PPI网络;利用Cytoscape软件对PPI网络进行拓扑分析得到核心靶点;利用DAVID数据库对核心靶点进行GO富集分析与KEGG通路富集分析,并对富集结果进行可视化分析。结合网络药理学预测结果,采用大鼠偏头痛模型,观察一粒金经鼻给药治疗偏头痛相关靶点的效果;采用ELISA法检测大鼠大脑皮层中一氧化氮(NO)、一氧化氮合酶(iNOS)、5-羟色胺(5-HT)、内皮素1(ET-1)、降钙素基因相关肽(CGRP)、瞬时受体电位香草酸亚型1(TRPV1)水平;RT-qPCR法检测大鼠大脑皮层及延髓中TRPV1 mRNA、谷氨酸受体5(mGluR5)mRNA表达水平。结果:一粒金中活性成分共计372个。偏头痛靶点共2346个,药物-疾病共同靶点共195个,关键靶点涉及PTGS2、MAPK1、ABCB1、AKT、BCL2、BDNF、CASP3、CCL2、EGFR、TRPV1等基因。GO功能富集分析条目147个,主要涉及肿瘤坏死因子(TNF)产生的正向调控、外周神经系统开发、炎症反应中细胞因子产生的正向调节等;KEGG通路富集分析得到155条路径,包括癌症通路、PI3K/AKT通路、AGE-RAGE信号通路、TNF信号通路、IL-17通路、HIF1通路、MAPK通路等通路。动物实验结果显示,一粒金能降低偏头痛模型大鼠大脑皮层中NO、iNOS、ET-1、CGRP、TRPV1水平,升高大脑皮层中5-HT水平,降低大脑皮层和延髓中mGluR5 mRNA、TRPV1 mRNA相对表达量。结论:一粒金具有治疗偏头痛的作用,其机制可能与TRPV1、mGluR5等关键因子相关。Objective:To explore the potential mechanism of intranasal administration of Yilijin(YLJ)in the treatment of migraine by means of network pharmacology and experimental verification.Methods:The active chemical constituents of YLJ and its related targets in the treatment of migraine were screened by TCM Systematic Pharmacology Database and Analysis platform(TCMSP).GeneCards database,OMIM database,UniProt database and TTD database were searched,and the target of migraine was obtained after summary and weight removal.The intersection method was used to obtain the related targets of YLJ and migraine.PPI network was constructed by STRING platform.The core target was obtained by topological analysis of PPI network according to Cytoscape software.GO enrichment analysis and KEGG pathway enrichment analysis were performed on the core target according to DAVID database,and the enrichment results were visually analyzed.According to the prediction results of network pharmacology,the effect of intranasal administration of YLJ on migraine related targets was observed in the rat model of migraine.The NO,iNOS,5-HT,ET-1,CGRP and TRPV1 in brain tissue were detected by ELISA.The expression of TRPV1 mRNA and mGluR5 mRNA were detected by RT-qPCR.Results:A total of 372 active ingredients were screened in YLJ.There were 2346 migraine targets and 195 drug-disease common targets.The key targets involved PTGS2,MAPK1,ABCB1,AKT,BCL2,BDNF,CASP3,CCL2,EGFR,TRPV1 and other genes.GO functional enrichment analysis included 147 GO items,which mainly involved the positive regulation of tumor necrosis factor production,peripheral nervous system development,and the positive regulation of cytokine production in inflammatory response.KEGG pathway enrichment analysis obtained 155 pathways,including cancer pathway,PI3K/AKT pathway,AGE-RAGE signaling pathway,TNF signaling pathway,IL-17 pathway,HIF1 pathway,MAPK pathway,etc.The results of experiments showed that YLJ could decrease the levels of NO,iNOS,ET1,CGRP and TRPV1 in brain tissue of migraine model ra

关 键 词：偏头痛 一粒金 滴鼻 网络药理学 瞬时受体电位香草酸亚型1 谷氨酸受体5 大鼠 

分 类 号：R285.5[医药卫生—中药学]