基于网络药理学探讨麝香通心滴丸治疗心力衰竭的潜在机制

目的应用网络药理学方法分析麝香通心滴丸治疗心力衰竭的潜在机制。方法利用中药系统药理学数据库与分析平台(TCMSP)、中药综合数据库(TCMID)筛选麝香通心滴丸潜在的活性成分与靶点,通过GeneCards数据库检索心力衰竭相关的靶点,采用STRING数据库构建共有靶点的蛋白互作网络,最后应用R Studio的clusterProfiler包进行基因本体(GO)与京都基因与基因组百科全书(KEGG)富集分析。结果根据口服生物利用度(OB)≥30%且类药性(DL)≥0.18为标准筛选出化合物92个有效成分。从GeneCards数据库中获得13194个与心力衰竭相关的靶基因,有效成分靶点与疾病靶点共筛选出140个共有基因。这些基因主要参与细胞对药物的反应、循环系统血管过程、对类固醇激素的反应、管径的调节、血管直径的调节等生物学过程。分子功能主要包括神经递质受体活性、G蛋白偶联氨受体活性、突触后神经递质受体活性、肾上腺素能受体活性等。活性物质主要作用于神经活动配体-受体相互作用、磷脂酰肌醇3-激酶-蛋白激酶B(PI3K-Akt)信号通路、人巨细胞病毒感染等通路。结论麝香通心滴丸中的有效成分可能通过调节血管直径、改变激素作用、改善代谢等机制对心力衰竭产生治疗作用。

Mechanism of Shexiang Tongxin Dropping Pill in the Treatment of Heart Failure Based on Network Pharmacology

Objective To explore the mechanism of Shexiang Tongxin Dropping Pill(STDP)in the treatment of heart failure(HF).Methods Traditional Chinese Medicines Systems Pharmacology Platform(TCMSP)and Traditional Chinese Medicine Integrated Database(TCMID)were used to screen the potential active ingredients and targets of STDP,and the related targets of HF were searched through GeneCards database.Protein-protein interaction(PPI)network with common targets was constructed by STRING database.Finally,gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis were carried out by clusterProfiler of R studio.Results Ninety-two active ingredients were screened according to oral bioavailability≥30%and drug similarity≥0.18.A total of 13194 target genes directly related to HF were obtained from GeneCards,and 140 common genes were screened from active component targets and disease targets.These genes were mainly involved in cellular response to vascular process in circulatory system,response to steroid hormone and regulation of tube diameter,regulation of blood vessel diameter.Molecular functions were mainly related to neurotransmitter receptor activity,G protein-coupled amine receptor activity,postsynaptic neurotransmitter receptor activity,adrenergic receptor activity.The active ingredients were related to neuroactive ligand-receptor interaction signaling pathway,phosphatidyl-inositol 3-kinase/serine-threonine kinase(PI3K-Akt)signaling pathway,human cytomegalovirus infection signaling pathway.Conclusion The effective ingredients of STDP may treat HF by regulating vascular diameter,changing hormone effect,and improving metabolism.