桃红四物汤治疗肢体缺血再灌注损伤的作用机制探讨

Discussion on the Mechanism of Taohong Siwu Decoction in the Treatment of Limb Ischemia-reperfusion Injury based on Network Pharmacology and Molecular Docking

目的:利用网络药理学与分子对接技术探讨桃红四物汤治疗肢体缺血再灌注损伤的作用机制,为临床治疗肢体缺血再灌注损伤提供一定的理论依据。方法:利用中药系统药理数据库和分析平台(TCMSP)得到桃红四物汤有效成分及其靶点信息,用Cytoscape3.8.2软件构建成分-靶点网络;通过GeneCards、OMIM数据库收集疾病相关靶点;运用STRING平台进行蛋白质相互作用分析,得到PPI网络,然后进行拓扑分析得到核心靶点;通过Metascape数据库进行GO和KEG通路富集分析,最后将主要有效成分与核心靶点进行分子对接。结果:共得到桃红四物汤的有效成分为69个,主要活性成分为槲皮素、木犀草素、山柰酚等,靶点基因240个,肢体缺血再灌注损伤靶点基因有1211个,交集基因133个;PPI网络分析得到ALB、TNF、AKT1、IL6、IL1B、VEGFA、TP53、PTGS2、GASP3、MMP9、EGF是桃红四物汤治疗肢体缺血再灌注损伤的核心靶点;GO分析包含生物过程(Biological Process,BP)1788个,包括对无机物的反应、对细胞运动的正向调节等;细胞组分(Cellular Components,CC)100个,包括膜筏、转录复合物等;分子功能(Molecular Functions,MF)152个,包括蛋白激酶激活、DNA结合转录因子等;KEEG通路分析得到202条信号通路,主要涉及到AGE-RAGE、TNF、IL-17等信号通路等;分子对接结果显示主要有效成分能与核心靶点结合,且具有较强的结合力。结论:桃红四物汤通过多种成分、多种靶点、多种通路作用于肢体缺血-再灌注损伤,为进一步研究桃红四物汤治疗肢体缺血再灌注损伤的机制,提供一定的理论依据。

Objective:To explore the mechanism of Taohong Siwu Decoction in the treatment of limb ischemia-reperfusion injury by using network pharmacology and molecular docking technology,so as to provide a certain theoretical basis for the clinical treatment of limb ischemia-reperfusion injury.Methods:The active ingredients and target information of Taohong Siwu Decoction were obtained by using the traditional Chinese medicine system pharmacology database and analysis platform(TCMSP),and the ingredient-target network was constructed with Cytoscape3.8.2 software;disease-related targets were collected through GeneCards and OMIM databases;The STRING platform conducts protein interaction analysis to obtain the PPI network,and then conducts topology analysis to obtain the core targets;conducts GO and KEG pathway enrichment analysis through the Metascape database,and finally carries out molecular docking of the main active ingredients with the core targets.Results:A total of 69 active ingredients of Taohong Siwu Decoction were obtained,the main active ingredients were quercetin,luteolin,kaempferol,etc.,240 target genes,and 1211 target genes for limb ischemia-reperfusion injury,with 133 intersection genes;PPI network analysis shows that ALB,TNF,AKT1,IL6,IL1B,VEGFA,TP53,PTGS2,GASP3,MMP9,and EGF are the core targets of Taohong Siwu Decoction in the treatment of limb ischemia-reperfusion injury;GO analysis Contains 1788 biological processes(Biological Process,BP),including responses to inorganic substances,positive regulation of cell movement,etc.;100 cellular components(Cellular Components,CC),including membrane rafts,transcription complexes,etc.;molecular Function(Molecular Functions,MF)152,including protein kinase activation,DNA binding transcription factors,etc.;KEEG pathway analysis obtained 202 signaling pathways,mainly involving AGE-RAGE,TNF,IL-17 and other signaling pathways;molecular docking results It shows that the main active ingredient can be combined with the core target,and has a strong binding force.Conclusion:Taohong Siwu Decoction acts on limb ischemia-reperfusion injury through multiple components,multiple targets,and multiple pathways,providing a certain theory for further research on the mechanism of Taohong Siwu Decoction in treating limb ischemia-reperfusion injury in accordance with.