防己黄芪汤治疗慢性心力衰竭作用机制的网络药理学探讨

The Mechanism of Fangji Huangqi Decoction in Treating Chronic Heart Failure by Network Pharmacology

目的基于网络药理学探讨防己黄芪汤治疗慢性心力衰竭的作用机制。方法通过中药系统药理学分析平台(TCMSP)检索防己黄芪汤中的有效成分和作用靶点,通过GeneCards和OMIM检索慢性心力衰竭的相关靶标基因,获取防己黄芪汤治疗慢性心力衰竭交集靶标基因,采用Cytoscape构建“药物-成分-疾病-靶点”网络,以Network analyzer插件进行网络分析,获取重要化合物和关键靶点;通过STRING构建蛋白质相互作用(PPI)网络;利用R语言clusterProfiler包进行基因本体(GO)功能富集分析和基于京都基因与基因组百科全书(KEGG)通路富集分析,注释识别基因功能和信号通路。结果防己黄芪汤中有156个有效成分,1174个作用靶点,与治疗慢性心力衰竭相关的靶标基因共113个,137个GO条目,35条信号通路,主要有磷脂酰肌醇-3-激酶/丝苏氨酸蛋白激酶(PI3K-Akt)信号通路、丝裂原活化蛋白激酶(MAPK)信号通路、细胞凋亡、肿瘤坏死因子(TNF)信号通路等。结论防己黄芪汤中的槲皮素、山柰酚等成分与毒蕈碱乙酰胆碱受体M(CHRM)、半胱氨酸蛋白酶(CASP)等靶蛋白结合,通过DNA结合转录、神经递质结合等过程以及PI3K-Akt、MAPK等信号通路,达到治疗慢性心力衰竭的作用。

Objective To explore the mechanism of Fangji Huangqi Decoction in the treatment of chronic heart failure based on network pharmacology.Methods Traditional Chinese Medicines Systems Pharmacology Platform(TCMSP)was used to search for the active ingredients and targets in Fangji Huangqi Decoction.GeneCards and OMIM were used to search for the related target genes of chronic heart failure.The"drug-component-disease-target"network was constructed by the software of Cytoscape.Network analysis was performed with Network Analyzer plug-in software to obtain important compounds and key targets.Protein-protein interaction(PPI)network was constructed by STRING.R language clusterProfiler package was used for Gene Ontology(GO)function enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Results There were 156 active ingredients and 1174 targets of Fangji Huangqi Decoction,and 113 target genes related to chronic heart failure,involving 137 GO entries and 35 signal pathway,including phosphoinositide 3-kinase-serine(PI3K)-threonine kinase(Akt)signaling pathway,mitogen-activated protein kinase(MAPK)signaling pathway,apoptosis,tumor necrosis factor(TNF)signaling pathway,etc.Conclusion Quercetin,kaempferol,and other components in Fangji Huangqi Decoction bind with target proteins such as muscarinic acetylcholine receptor M and caspase to treat chronic heart failure through DNA binding transcription,neurotransmitter binding,and PI3K-Akt,MAPK and other signaling pathways.