基于网络药理学分析补气养血通络组方对硼替佐米诱导的周围神经病变机制

Analysis of the Potential Mechanism of Buqi-Yangxue-Tongluo in the Treatment of Bortezomib Induced Peripheral Neuropathy Based on Network Pharmacology Method

目的探讨补气养血通络组方治疗硼替佐米诱导的周围神经病变的潜在作用机制。方法利用中药系统药理学数据库与分析平台,筛选出补气养血通络组方中黄芪、桂枝、白芍、生姜、大枣、鸡血藤、路路通、丹参的有效活性成分,并通过GeneCards数据库和OMIM数据库获取硼替佐米诱导的周围神经病变(bortezomib-induced peripheral neuropathy,BIPN)的相关靶点基因,两者取交集得到药物潜在作用靶点基因。运用Cytoscape-3.8.0构建中药—活性成分—靶点—疾病网络关系。利用STRING数据库构建蛋白互作网络图,依托R 4.1.2进行GO功能富集分析和KEGG通路富集分析。通过分子对接技术,对重要靶点及有效成分进行分析。结果共筛选出药物活性成分139种。药物潜在作用靶点基因255个,BIPN相关靶点基因815个,两者取交集获得共同靶点97个,其中前10位基因为TP53、AKT1、MAPK14、FOS、RELA、MYC、STAT3、CTNNB1、ESR1、MAPK1。KEGG通路富集分析主要涉及PI3K-Akt信号通路、MAPK信号通路、NF-κB信号通路等与治疗BIPN相关的信号通路。槲皮素与TP53和AKT1之间有良好的亲和力。结论补气养血通络组方含有多种活性成分,通过多途径、多靶点发挥治疗硼替佐米诱导的周围神经病变的作用。

Objective To explore the potential mechanism of Buqi-Yangxue-Tongluo in the treatment of bortezomib induced peripheral neuropathy.Methods The pharmacology database and analysis platform of traditional Chinese medicine system were used,the active ingredients of Astragalus,Guizhi,Paeonia lactiflora,Ginger,Jujube,Jixueteng,Lulutong and Salvia miltiorrhiza were screened out in the Buqi-Yangxue-Tongluo.The relevant target genes of bortezomib-induced peripheral neuropathy(BIPN)were obtained from the GeneCards database and the OMIM database,and the potential target genes of the drug were obtained by taking the intersection of the two.Cytoscape software version 3.8.0 was used to construct the network relationship of traditional Chinese medicine-active ingredients-target-disease.The STRING database was used to construct a protein interaction network map,and R software version 4.1.2 was used for GO function enrichment analysis and KEGG pathway enrichment analysis.Molecular docking technology was also used to analyze important targets and effective components.Results A total of 139 active pharmaceutical ingredients were screened out.There were 255 potential drug target genes and 815 BIPN-related target genes.The intersection of the two was 97 common targets,of which the top ten genes were TP53,AKT1,MAPK14,FOS,RELA,MYC,STAT3,CTNNB1,ESR1,MAPK1.KEGG pathway enrichment analysis mainly involved PI3K-Akt signaling pathway,MAPK signaling pathway,NF-κB signaling pathway and other signaling pathways related to the treatment of BIPN.Additionally,Quercetin was found to have good affinity with TP53 and AKT1.Conclusion Buqi-Yangxue-Tongluo contains a variety of active ingredients,which play a role in the treatment of bortezomib-induced peripheral neuropathy through multiple pathways and multiple targets.