基于网络药理学-分子对接-Meta分析探讨灯盏细辛治疗POAG的作用机制  

Discussion on the mechanism of Erigeron breviscapus in the treatment of primary open angle glaucoma based on network pharmacology,molecular docking and Meta analysis

作　　者：孙志超 张丽霞[1,2] 魏宇娇[1] 倘孟莹 陈文黎 陈爽 SUN Zhichao;ZHANG Lixia;WEI Yujiao;TANG Mengying;CHEN Wenli;CHEN Sh-uang(Eye Hospital,China Academy of Chinese Medical Sciences,Beijing 100040,China)

机构地区：[1]中国中医科学院眼科医院,北京100040 [2]中国中医科学院,北京100700 [3]浙江中医药大学附属温州中西医结合医院,温州325001

出　　处：《中国中医眼科杂志》2023年第5期485-494,共10页China Journal of Chinese Ophthalmology

基　　金：国家自然科学基金面上项目(82074500);北京市自然科学基金面上项目(7212197);中国中医科学院科技创新工程重大攻关项目(CI2021A02605);首都卫生发展科研专项重点攻关项目(2018-1-4181);中国民族医药学会科研项目(2020ZY356-320301)。

摘　　要：目的基于网络药理学及分子对接探讨灯盏细辛治疗原发性开角型青光眼(POAG)的活性成分、作用靶点、基因功能及信号通路,并结合Meta分析验证灯盏细辛在POAG的有效性。方法通过中药系统药理学数据库与分析平台(TCMSP)对灯盏细辛的有效成分及作用靶点进行初步预测,使用Uniprot数据库对靶点信息进行标准化;通过GeneCards、DrugBank、OMIM、DisGeNET、TTD数据库对POAG靶点进行筛选,将药物靶点及疾病靶点进行整合取交集得到灯盏细辛治疗POAG的关键靶点信息,并用Venn图表示;通过String数据库与Cytoscape软件对关键靶点构建蛋白互作网络(PPI),运用R语言对关键靶点进行分析得到核心靶点,并对交集靶点进行基因本体功能分析(GO)及京都基因和基因组百科全书(KEGG)富集分析。选取灯盏细辛中的木犀草素、槲皮素等5种关键活性成分和核心靶点通过Discovery Studio2019(DS2019)软件进行分子对接验证;基于Meta分析验证灯盏细辛治疗慢性高眼压模型动物模型在眼压、视网膜神经节细胞(RGC)凋亡的影响。结果(1)靶点:灯盏细辛治疗POAG的作用靶点共有102个,核心靶点有丝氨酸/苏氨酸蛋白激酶(AKT),肿瘤坏死因子(TNF),白细胞介素-6(IL-6)等。(2)信号通路:主要包括脂质与动脉粥样硬化、流体切应力与动脉粥样硬化、糖尿病并发症相关的晚期糖基化终产物及其受体(AGE-RAGE)信号通路、白细胞介素-17(IL-17)信号通路、低氧诱导因子-1(HIF1)信号通路、磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/Akt)信号通路等。(3)分子对接:灯盏细辛的核心基因与成分有较好的结合活性。(4)Meta分析:灯盏细辛可有效降低慢性高眼压模型大鼠眼压,减少RGC的凋亡。结论灯盏细辛通过多靶点、多通路参与化学性应激、氧化应激及细胞凋亡等生物学过程治疗POAG,体内实验及分子对接验证均证明灯盏细辛可有效治疗POAG,该研究为临床中应�OBJECTIVE To explore the active in⁃gredients,targets,gene functions,and signaling pathways of Erigeron breviscapus in the treatment of primary openangle glaucoma(POAG)using network pharmacology and molecular docking,and to validate its effectiveness of Erigeron breviscapus in POAG treatment through Metaanalysis.METHODS The effective ingredients and tar⁃gets of Erigeron breviscapus were preliminarily predicted through the Traditional Chinese Medicine Systems Phar⁃macology Database and Analysis Platform(TCMSP),and the target information was standardized using the Uniprot database;POAG targets were screened through GeneCards,DrugBank,OMIM,DisGeNET,and TTD databases,and the key target information for Erigeron breviscapus in the treatment of POAG was obtained through the integrating and intersection of drug targets and disease targets,which was represented with Venn diagrams;The key targets were used to construct a protein-protein interaction(PPI)network through String database and Cytoscape software,and R language was used to analyze those key targets to obtain core targets.Also,Gene Ontology(GO)and Kyoto En⁃cyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed on the overlapping targets.A total of five key active ingredients and core targets of Erigeron breviscapus,including quercetin and isorhamnetin,were vali⁃dated through molecular docking using Discovery Studio 2019(DS2019)software;Meta-analysis was used to verify the effects of Erigeron breviscapus on intraocular pressure and retinal ganglion cell(RGC)apoptosis in chronic ocu⁃lar hypertension animal models.RESULTS(1)Targets:There were a total of 102 targets for the treatment of POAG with Erigeron breviscapus,with core targets including serine/threonine protein kinase(AKT),tumor necrosis factor(TNF),interleukin-6(IL-6),etc.(2)Signaling pathways:The main signaling pathways included(advanced glycation endproduct/the receptor of advanced glycation endproducts)AGE-RAGE signaling pathway,interleukin-17(IL-17)signaling pathway,hypoxia-ind

关 键 词：网络药理学 分子对接 灯盏细辛 原发性开角型青光眼 

分 类 号：R285.5[医药卫生—中药学]