丹参治疗缺血性脑卒中潜在效应机制的网络药理学研究

The Mechanism of Salvia Miltiorrhiza for Ischemic Stroke Based on Network Pharmacology

目的通过网络药理学分析方法,探究丹参治疗缺血性脑卒中的潜在效应机制,为其进一步开发和应用提供参考。方法通过网络药理学分析平台(BATMAN-TCM)数据库获取丹参化学成分及成分预测靶标,从DisGeNET、NCBI、HPO、Gene Cards数据库筛选缺血性脑卒中的疾病靶标。利用STRING数据库进行丹参成分靶标-缺血性脑卒中疾病靶标的蛋白互作网络分析,根据网络拓扑分析结果进一步筛选出丹参治疗缺血性脑卒中的核心靶标,对核心靶标进行基因本体(GO)分析和京都基因和基因组百科全书(KEGG)通路富集分析。结果经筛选共获取丹参成分38种,成分预测靶标770个,缺血性脑卒中疾病靶标1216个。丹参治疗缺血性脑卒中的核心靶标83个,包括白介素6(IL-6)、肿瘤坏死因子(TNF)、TP53、SRC、白介素1β(IL-1β)、FOS、PTGS2、EDN1、JUN、白介素10(IL-10)等基因,参与了一氧化氮生物合成、炎症反应、衰老、血压调节等生物学过程,主要富集在TNF信号通路、环磷酸腺苷(cAMP)信号通路、丝裂原活化蛋白激酶(MAPK)信号通路、Toll样受体信号通路等多条信号通路。结论丹参治疗缺血性脑卒中具有多靶点、多通路的效应机制,其机制与炎症反应、细胞因子调控等密切相关。

Objective To probe the underling mechanisms of Salvia Miltiorrhiza(SM)for treating ischemic stroke(IS)using a network pharmacology approach.Methods The active components and target of SM were obtained through the BATMAN-TCM and the disease target of IS was screened from DisGeNET,NCBI,HPO and Gene.The STRING database was used to do protein interaction network analysis of danshen component target-ischemic stroke disease target and get the core target for further analysis of Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway.Results A total of 38 components and 770 predicted targets of SM were obtained,with 1216 disease targets.And at last 83 key targets of SM for treating IS were acquired,such as interleukin-6,TNF,TP53,SRC,interleukin-1β,FOS,PTGS2,EDN1,JUN,interleukin-10,which were involved in the biological processes of nitric oxide biosynthesis,inflammatory response,senescence,blood pressure regulation,and were mainly enriched in multiple signaling pathways,such as tumor necrosis factor signaling pathway,cyclic adenosine monophosphate signaling pathway,mitogen-activated protein kinase signaling pathway,Toll-like receptor signaling.Conclusion The mechanism of SM for IS is multi-target,multi-pathway,which is closely related to inflammatory response,cytokine regulation.