基于网络药理学研究黄芪治疗逼尿肌无力的作用机制

Mechanism of astragalus mongholicus treating detrusor muscle weakness based on network pharmacology

目的采用网络药理学技术预测黄芪有效成分在治疗膀胱逼尿肌无力的主要作用靶点及相关信号通路。方法通过检索中药系统药理学数据库与分析平台(TCMSP)获取黄芪相关的有效化学成分和作用靶点,运用GeneCards数据库筛选逼尿肌无力相关靶点。采用Cytoscape软件构建药物-靶点-基因-疾病之间相互作用的网络关系并进行分析。基于STRING数据库绘制治疗靶点间蛋白相互作用的PPI网络。运用R软件对疾病与药物交集靶点进行GO生物学过程富集分析和KEGG通路注释分析。结果预测得到黄芪有效成分11种,关键靶点17个,并通过通路富集分析推测黄芪治疗膀胱逼尿肌无力的作用机制可能和钙信号通路、PI3K-Akt信号通路、Neuroactive配体-受体相互作用、细胞衰老等信号通路有关,并发现白介素-6、雄激素受体、细胞周期蛋白D1、酪氨酸激酶受体2等靶点基因可能在治疗膀胱逼尿肌无力中起到关键作用。结论通过网络药理学分析,预测黄芪可能通过多成分、多靶点的方式作用于膀胱逼尿肌,为研究治疗膀胱逼尿肌无力药物提供了新的理论依据。

Objective To predict the main targets and related signaling pathways of active ingredients of astragalus mongholicus in the treatment of detrusor muscle weakness by network pharmacology.Methods Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)was used to obtain the active ingredients and main targets of astragalus mongholicus.GeneCards database was used to obtain the main targets of detrusor muscle weakness.Cytoscape was used to construct and analyze the network relationship of drug target gene disease interaction.The PPI network of therapeutic targets was drawn based on STRING database.R software was utilized for GO functional enrichment analysis and KEGG pathway annotation analysis on the intersected targets of disease and drug.Results A total of 11 active ingredients and 17 key targets of astragalus mongholicus were predicted,and the mechanism of action of astragalus mongholicus on detrusor muscle weakness was speculated through pathway enrichment analysis,which might be related to calcium signaling pathway,PI3K-Akt signaling pathway,Neuroactive ligand receptor interaction,and cellular senescence.In addition,interleukin-6,androgen receptor,cyclin D1,tyrosine kinase receptor 2 and other targets were found to play key roles in the treatment of detrusor muscle weakness.Conclusion Through the network pharmacological analysis,we speculate that astragalus mongholicus may act on detrusor muscle weakness in a multi-component and multi-target way,which provides a new theoretical basis for the treatment of detrusor muscle weakness.