基于网络药理学探讨补肾活血中药治疗退行性腰椎失稳症的作用机制研究

Study on the Mechanism of Bushen Huoxue Decoction on Degenerative Lumbar Spinal Instability based on Network Pharmacology

目的探讨补肾活血中药治疗退行性腰椎失稳症(Degenerative Lumbar Spinal Instability,DLSI)的关键靶点以及作用机制。方法通过TCMSP数据库筛选补肾活血常用中药熟地、牛膝、当归、威灵仙和三七的有效成分、潜在靶点;通过Gene Cards、OMIM等数据库搜集DLSI的疾病靶点;两者取交集得到的药物与疾病的共有靶点。应用Cytoscape软件构建"补肾活血中药—成分—靶点—疾病"网络图;使用STRING数据库绘制蛋白互作(PPI)网络图,对关键靶点进行GO富集分析以及KEGG通路富集分析。结果补肾活血中药有效活性成分31个,潜在靶点51个;DLSI疾病靶点1236个;药物疾病共有靶点22个。PPI网络提示IL6、VEGFA、MAKP8、EGFR、ESR1、AR等可能是补肾活血中药治疗DLSI的核心靶点。GO富集分析得到63个细胞生物学条目,主要涉及核受体活性、雌激素、β连环蛋白结合、类固醇激素受体、类固醇结合、激素结合等;KEGG通路富集分析得到54条相关信号通路,主要有Prostate cancer、AGE-RAGE signaling pathway in diabetic complications、HIF-1 signaling pathway等。结论补肾活血中药治疗DLSI是多靶点、多通路及多层次的,为进一步研究分子生物学验证提供了思路与依据。

Objective To explore the key target and mechanism of Bushen Huoxue Chinese medicine in the treatment of Degenerative Lumbar Spinal Instability(DLSI).Methods TCMSP database was used to screen the effective components and potential targets of Shudi,Niuxi,Danggui,Weilingxian and Sanqi in Bushenhuoxue decoction.Gene Cards and OMIM database were used to collect the disease targets of DLSI.The network diagram of"Bushenhuoxue decoction-Ingredients-Target-Disease"was constructed by using the software of Cytoscape;the network diagram of proteins interaction(PPI)was drawn by using the STRING database,and the enrichment analysis of GO and KEGG pathway was carried out for the key targets.Results There were 31 active components and 51 potential targets in Bushenhuoxue decoction,1236 disease targets of DLSI,22 common targets of drugs-diseases.PPI network suggests that IL6,VEGFA,makp8,EGFR,ESR1,AR and so on may be the core target of Bushenhuoxue decoction in the treatment of DLSI.63 cell biological items were obtained by GO enrichment analysis,mainly involving Nuclear receptor activity,Estrogen,β-Catenin binding,Steroid hormone receptor,Steroid binding,Hormone binding,etc.The analysis of KEGG pathway enrichment shows that there are 54 related signal pathways,including Prostate cancer,AGE-RAGE signaling pathway in diabetic complications,HIF-1 signaling pathway and so on.Conclusion Bushen Huoxue Decoction is multi-target,multi-channel and multi-level in the treatment of DLSI,which provides ideas and basis for further study of molecular biological verification.