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目的：通过网络药理学构建多靶点互相作用网络来揭示六味地黄丸治疗勃起功能障碍（ED）的机制。方法：从中药系统药理学数据库与分析平台（TCMSP）预测出六味地黄丸的有效活性成分及它可能与机体结合的潜在靶点，通过TTD、OMIM、DrugBank、GeneCards等数据库检索与ED相关的基因，通过Cytoscape软件绘制中药复方调控网络。将六味地黄丸潜在靶点和ED相关基因的交集基因导入string得到蛋白互作网络（PPI），再获得它的核心PPI。绘制GO、KEGG富集分析气泡图以及相关的通路图。用vina软件将药物主要有效成分和核心靶点完成分子对接。结果：筛选出六味地黄丸的39个化学成分，190个潜在作用靶点。和ED相关的基因共1 164个。这些关键靶点主要有JUN、AKT1、CASP3、VEGFA、TP53，涉及的通路主要包括脂质和动脉粥样硬化信号通路、PI3K-Akt信号通路、人巨细胞病毒感染信号通路、AGE-RAGE信号通路等。结论：六味地黄丸通过多组分、多靶点和多途径治疗ED。
Abstract：Objective:To investigate the mechanism of Liuwei Dihuang Pills(LWDHP)in the treatment of erectile dysfunction(ED)via network pharmacological study.Methods:The Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP)was used to predict the active ingredients of LWDHP and its potential targets that may bind to the body. Internet search in databases including Therapeutic Target Database(TTD),Online Mendelian Inheritance in Man(OMIM),DrugBank,and GeneCards was performed to identify studies on ED-related genes. Cytoscape software was used to generate a traditional Chinese medicine(TCM)compound-disease regulatory network. The intersection between the potential targets of LWDHP and ED-related genes were imported into the Search Tool for Retrieval of Interaction Gene/Proteins(STRING)database to generate a protein-protein interaction(PPI)network,and then its core PPI was obtained.The bubble charts of Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,and the related pathway charts were generated.Molecular docking between the main active ingredients and the core targets was completed via the Vina software.Results:A total of 39 chemical constituents and 190 potential targets of LWDHP were screened out,and 164 ED-related genes were obtained.The core targets included JUN,AKT1,CASP3,VEGFA,and TP53.The enriched signaling pathways included lipid and atherosclerosis,PI3K-Akt,human cytomegalovirus infection,and AGE-RAGE signaling pathways.Conclusion:LWDHP works via multiple components,multiple targets and multiple pathways in treatment of ED.
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基本信息:
中图分类号:R285
引用信息:
[1]徐然,张金虎,侯佳茂,等.基于网络药理学研究六味地黄丸治疗勃起功能障碍的作用机制[J].广州医科大学学报,2022,50(04):19-27.
2022-08-15
2022-08-15