基于网络药理学和分子对接技术探讨“川芎–当归”治疗急性缺血性脑卒中的作用机制

Based on Network Pharmacology and Molecular Docking, the Mechanism of “Angelica sinensis-Chuanxiong” in Treating Acute Ischemic Stroke Was Analyzed

摘要: 目的：本文运用计算机网络药理学和分子对接技术，预测川芎–当归药对治疗急性缺血性脑卒中的作用机制。方法：通过TCMSP数据库筛选出川芎和当归的有效成分及相关靶点，通过检索GeneCard、OMIM、DrugBank和Disgenet数据库，获得相关目标。利用Venny2.1绘制韦恩图获取药物疾病共同靶点，将其输入Cytoscape3.9.1软件绘制“当归、川芎–共同靶点–急性缺血性脑卒中”网络图。运用STRING数据库及Cytoscape3.9.1软件构建蛋白相互作用PPI网络，通过DAVID数据库进行靶点本体(GO)、京都靶点与靶点组百科全书(KEGG)富集分析，用微生信做富集分析的气泡图。利用AutoDock软件对分子对接进行了验证，并用pymol软件对分子对接进行了可视化。结果：分析出当归、川芎治疗急性缺血性脑卒中的有效活性成分9个，且潜在作用靶点53个，关键作用靶点为JUN、ESR1、CASP3、PTGS2。结论：当归、川芎药对通过多种通路、多种有效活性成分、多种有效靶点、实现对于急性缺血性脑卒中的治疗。主要涉及钙信号通路、磷脂酰肌醇-3-激酶(Phosphatidylinositol 3-kinase, PI3K)-AKT通路等通路发挥治疗作用，为后续研究此药对治疗急性缺血性脑卒中的机制提供了理论支持。

Abstract: Objective: In this paper, computer network pharmacology and molecular docking techniques were applied to predict the mechanism of action of Chuanxiong and Angelica sinensis in the treatment of acute ischaemic stroke. Methods: The active ingredients and related targets of Chuanxiong and Angelica sinensis were screened by TCMSP database, and the related targets were obtained by searching GeneCard, OMIM, DrugBank and Disgenet databases. The Venny2.1 Venn diagram was used to obtain the common targets of the drugs and diseases, and then entered into the Cytoscape 3.9.1 software to draw the network diagram of “Angelica sinensis and Rhizoma Ligustici Chuanxiong - common targets - acute ischaemic stroke”. The protein interaction PPI network was constructed by using STRING database and Cytoscape 3.9.1 software, and the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were carried out through DAVID database, and the bubble diagrams of the enrichment analyses were made by using Microbiology Letter. The molecular docking was verified by AutoDock software and visualised by Pymol software. Result: Nine active ingredients and 53 potential targets of Angelica sinensis and Rhizoma Ligustici Chuanxiong in the treatment of acute ischemic stroke, and the key targets were JUN, ESR1, CASP3 and PTGS2. Conclusion: The pair of Angelica sinensis and Rhizoma Ligustici Chuanxiong can be used in the treatment of acute ischemic stroke through a variety of pathways, active ingredients and targets. The therapeutic effects of this drug on acute ischaemic stroke are mainly related to the calcium signaling pathway and the phosphatidylinositol 3-kinase (PI3K)-AKT pathway, which provides theoretical support for the subsequent study of the mechanism of this drug in the treatment of acute ischaemic stroke.