丹参酮ⅡA治疗增生性瘢痕的网络药理学研究

A Predictive Study of Target and Mechanism of Tanshinone ⅡA in Treatment of Hypertrophic Scar Based on Network Pharmacology

目的利用网络药理学技术对丹参酮ⅡA(TanⅡA)治疗增生性瘢痕(HS)进行生物分子网络分析,预测其作用靶点及机制。方法利用中药系统药理学分析平台(TCMSP)和Genecards数据库收集整合TanⅡA相关靶点数据,经Genecards数据库和DisCeNET数据库收集筛选HS靶点数据;采用Cytoscaβe 3.6.1软件构建TanⅡA治疗HS的"成分-靶点"网络、"疾病-靶点"网络以及"成分-靶点-疾病"网络;利用STRING数据库构建靶蛋白相互作用(PPI)网络,根据度值和介数筛选出关键靶蛋白;利用BINGO和MCODE插件对潜在靶点进行Gene Ontology(GO)生物过程富集和聚类分析;利用R软件3.5.3版中的clusterProfiler 3.8程序包对靶点进行KEGG信号通路富集分析。结果共筛选出56个潜在作用靶点,发现其中IL-6、VEGFA、TNF、TGF-β1、AKT1、TP53、EGFR等19个关键靶点;GO生物进程分析共包含1 085条富集结果,聚类分析后得到蛋白激酶级联反应、毛囊发育、内环境稳态等40个子簇;KEGG信号通路富集主要涉及TNF、PI3K-Akt、MAPK等137条信号通路。结论 TanⅡA可能通过多靶点、多途径对HS发挥治疗作用,可为丹参治疗HS提供候选靶标和候选药物。

Objective To analyze the biomolecular network of Tanshinone Ⅱ A(Tan Ⅱ A) in the treatment of hypertrophic scar(HS) based on network pharmacology and to predict its target and mechanism.Methods The target data of Tan Ⅱ A were collected from TCMSP database and Genecards database,and the target data of HS were screened from Genecards database and DisGeNET database.The "component-target" network, "disease-target" network and "component-target-disease" network of Tan Ⅱ A in the treatment of HS were constructed using Cytoscape 3.6.1 software.Besides,STRING database was used to construct the PPI network and the key target proteins were screened according to their degree and betweenness.Gene Ontology(GO) biological process enrichment and clustering analysis of potential targets were performed by BINGO and MCODE plug-ins.The Enrichment of KEGG signaling pathways were analyzed by ClusterProfiler 3.8 package in R software 3.5.3.Results A total of 56 potential targets were screened,among which 19 key targets were found,such as IL6,VEGFA,TNF,AKT1,TP53,and EGFR.The GO biological process analysis included 1 085 enrichment results,and after cluster analysis,40 sub-clusters,such as protein kinase cascade reaction,hair follicle development,and internal environment homeostasis and so on,were obtained.The enrichment of KEGG signaling pathway was mainly involved in TNF,PI3 K-Akt and MAPK signaling pathways.Conclusion This study provided candidate targets and drug of Salviae miltiorrhiza radix et rhizoma for the treatment of HS.