摘要
目的通过网络药理学方法,揭示脉通饮治疗冠心病(CHD)的作用机制。方法借助中药系统药理学数据库与分析平台(TCMSP),将口服生物利用度(OB)与类药性(DL)当做限定条件,完成对脉通饮所含药物化学组分与其蛋白靶点的筛选,同时参考数据库UniProt,对蛋白靶点对应的基因名称加以明确。经由在线人类孟德尔遗传数据库(OMIM)、治疗靶标数据库(TTD),完成对CHD相关基因的检索。双方取交集后,再借助蛋白质相互作用数据库(STRING)建立蛋白互作网络,接着由Cytoscape辅助,对网络核心靶点展开分析,构建“疾病/中药/化合物/靶点”网络,根据string平台导出的数据通过R语言分析其治疗CHD的关键靶点,借助数据库bioconductor开展基因本体(GO)富集分析及KEGG通路富集分析。结果由网络药理学法辅助,自脉通饮筛选出活性成分共计116个,借助Venn分析疾病相关靶点,从而明确出143个药物潜在作用基因。分析网络中的拓扑参数,筛选出排名前20位的关键靶点,包括蛋白激酶B1(Akt1)、白介素6(IL-6)、丝裂原活化蛋白激酶8(MAPK8)、肿瘤坏死因子(TNF)、基质金属蛋白酶2(MMP-2)等核心靶点。经ClueGO富集分析关键靶点主要被富集在TNF信号通路、MAPK信号通路、PI3K-Akt信号通路等。结论脉通饮可能是通过影响Akt1、IL-6、MAPK8、TNF、MMP-2等靶点,调控TNF、MAPK、PI3K-Akt等通路对CHD发挥作用。
ObjectiveTo reveal the therapeutic mechanism of Maitong Yin for coronary heart disease(CHD).MethodsBy means of traditional Chinese medicine system pharmacology database and analysis platform(TCMSP),the medicinal chemical components and protein targets contained in Maitong Yin were screened by taking oral bioavailability(OB)and drug-like properties(DL)as the limiting conditions,and the names of genes corresponding to the protein targets were clarified by referring to the database UniProt.A search of CHD-related genes was completed through Online Mendelian Inheritance in Man(OMIM)and Therapeutic Target Database(TTD).After taking the intersections,the protein interaction network was established by using STRING(protein interaction database),and then the core targets of the network were analyzed with the help of Cytoscape,so that a"disease/Chinese medicine/compound/target"network was constructed.In the data derived from the string platform,the key targets for treating CHD were explored in R,the gene ontology(GO)enrichment analysis was conducted via database bioconductor,and pathway enrichment analysis was carried out through Kyoto Encyclopedia of Genes and Genomes(KEGG).ResultsUsing the network pharmacology method,a total of 116 active ingredients were screened from Maitong Yin,and the disease-related targets were analyzed through Venn.In this way,143 potential action genes were identified,and the top 20 key targets were selected by analyzing topological parameters in the network,including protein kinase B1(Akt1),interleukin(IL)-6,mitogen-activated protein kinase(MAPK)8,tumor necrosis factor(TNF),and matrix metalloproteinase(MMP)-2.The ClueGO enrichment analysis showed that the key targets were mainly enriched in the TNF signaling pathway,MAPK signaling pathway,and PI3K-Akt signaling pathway.ConclusionThe therapeutic mechanism of Maitong Yin for CHD may be affecting targets such as Akt1,IL-6,MAPK8,TNF,and MMP-2,and regulating the TNF,MAPK,and PI3K-Akt signaling pathways.
作者
陈弦
孔俊虹
沙晨曦
龚楚桥
Chen Xian;Kong Junhong;Sha Chenxi;Gong Chuqiao(Department of Cardiovascular Medicine,Changzhou Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine,Changzhou 213003,China;Cure Disease Center,Changzhou Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine,Changzhou 213003,China)
出处
《中华临床医师杂志（电子版）》
CAS
北大核心
2021年第11期882-889,共8页
Chinese Journal of Clinicians(Electronic Edition)
基金
江苏省中医药局重点项目(ZD201709)
常州市卫健委青年人才科技项目(QN201937)
关键词
网络药理学
脉通饮
冠心病
Network pharmacology
Maitong Yin
Coronary heart disease
