目的 基于网络药理学和生物信息学挖掘补肾活血胶囊的活性成分靶点和骨质疏松症的靶点,探究补肾活血胶囊抗骨质疏松的分子机制.方法 通过采用网络药理学和生物信息学的相关手段,对补肾活血胶囊进行活性成分筛选、药物疾病靶点预测,明确补肾活血胶囊防治骨质疏松症的特异性靶点,分析其信号通路富集程度以探究其分子机制.结果 通过TCMSP数据库检索共发现补肾活血胶囊相应成分1186个,根据OB值和DL值筛选出入血活性成分249个,在此基础上获得其预测靶点145个.通过二次挖掘GEO数据库的基因芯片筛选出明显的差异基因124个;检索疾病基因相关数据库共发现与骨质疏松症发生发展相关的已知的靶点基因356个.通过cytoscape 构建并结合网络拓扑分析共筛选出关键基因229个;利用ClueGO富集分析显示,补肾活血胶囊除与直接作用于骨质疏松症关键节点涉及的信号通路,如Wnt信号通路、TGF-β信号通路和Notch信号通路等有关,还对P13 K-AKT信号通路、VEGF信号通路和甲状腺素信号通路等同时进行调控.结论 补肾活血胶囊治疗骨质疏松症具有多成分、多靶点的特点;其主要通路不仅直接参与骨重建的细胞分化,调节成骨、破骨代谢平衡,还通过全身其他系统,如循环系统、神经系统等来干预和影响骨微环境,与目前抗骨质疏松的作用机制相符合.%Objective To investigate the molecular mechanism of nourishing kidney and promoting blood circulation capsule and its predictive and key targets on the treatment of osteoporosis based on network pharmacology and bioinformatics.Methods The method of network pharmacology and bioinformatics was used to determine and to screen the known compounds corresponding to nourishing kidney and promoting blood circulation capsule, to predict the drug-related gene/protein targets, to analyze the signal pathway enrichment, and to further analyze the molecular mechanism of nourishing kidney and promoting blood circulation capsule. Results 1186 corresponding compounds of nourishing kidney and promoting blood circulation capsule were retrieved from the TCMID database.According to the values of OB and DL, 249 blood promoting components were screened, and 145 predicting targets were obtained.Through the secondary mining of the gene chip of GEO chip database, 124 significantly different genes were obtained.A total of 356 known target genes closely related to the development of osteoporosis were retrieved from the disease-related database.Using the cytoscape to construct and synthesize the protein-protein interaction network of active ingredients and diseases, 229 key genes were screened out by network topological analysis.Using ClueGO analysis, it is shown that nourishing kidney and promoting blood circulation capsule was directly involved in the signal pathways of the key points of osteoporosis, which were mainly related to the direct regulation of bone metabolism, such as Wnt signaling pathway, TGF-signaling pathway, Notch signaling pathway, P13 K-AKT signaling pathway, VEGF signaling pathway, and thyroid hormone signaling pathway.Conclusion Nourishing kidney and promoting blood circulation capsule has the characteristics of multiple targets and multicomponent in the treatment of osteoporosis.It is not only directly involved in bone cell differentiation and regulation of the balance of osteogenesis and osteoclasts, but also affects and interferes with the bone microenvironment through other systemic systems, such as circulatory system, nervous system, which is consistent with the current mechanism of osteoporosis treatment.
展开▼
