基于网络药理学探讨盐酸雷洛昔芬治疗绝经后骨质疏松症的作用机制

AStudy on the Mechanism of Raloxifene Hydrochloride in Treatment of Postmenopausal Osteoporosis Based on Network Pharmacology

目的:运用网络药理学研究盐酸雷洛昔芬治疗绝经后骨质疏松症潜在的作用靶点和作用机制。方法:通过GeneCards数据库收集盐酸雷洛昔芬与绝经后骨质疏松症的靶点,共同靶点的交集通过Venny 2.1工具获得,采用STRING数据库构建共同靶点的PPI(Protein-Protein Interation,PPI),使用可视化软件Cytoscape 3.9.1的McCreight算法(MCC)对PPI进行分析,筛选出排名前10的中枢基因(Hub genes),通过DAVID生物信息学资源数据库进行GO生物功能、KEGG通路富集分析。结果:筛选出药物与疾病有168个共同靶点;关键靶点涉及STAT3、SRC、MAPK1、ESR1、JUN、PIK3R1、FOS、SP1、MAPK14和MYC等。盐酸雷洛昔芬可能通过调节STAT3、SRC、MAPK1、ESR1和JUN等关键基因,内分泌抵抗通路、糖尿病并发症晚期糖基化终末产物受体(AGE-RAGE)信号通路、脂质与动脉粥样硬化通路、与磷脂酰肌醇相关的PI3K-Akt信号通路等治疗绝经后骨质疏松症。结论:本文预测了盐酸雷洛昔芬治疗绝经后骨质疏松症的作用靶点和信号通路,可为下一步实验研究和研究方向奠定基础。

Objective:To explore the potential targets and mechanisms of hydrochloride raloxifene in treatment of postmenopausal osteoporosis based on network pharmacology.Methods:The protein targets of hydrochloride raloxifene and the corresponding targets of postmenopausal osteoporosis are obteined by GeneCards database,and the common targets of hydrochloride raloxifene and postmenopausal osteoporosis are screened out through Venny 2.1 software.The protein-protein interaction(PPI)network of the action targets is constructed through STRING database,and the top ten hub genes are screened using the McCreight algorithm (MCC) by Cytoscape 3.9.1 software. GO and KEGG gene enrichment analysis is performed by the DAVID bioinformatics resource database. Results: 168 common protein targets of hydrochloride raloxifene and postmenopausal osteoporosis are screened out, including STAT3, SRC, MAPK1, ESR1, JUN, PIK3R1, FOS, SP1, MAPK14, MYC, etc. Hydrochloride raloxifene may regulate key genes such as STAT3, SRC, MAPK1, ESR1, JUN and others to control various signaling pathways, including cancer pathways, endocrine resistance pathways, AGE-RAGE signaling pathways in diabetic complications, lipid and atherosclerosis pathways, PI3K-Akt signaling pathways, etc. Conclusion: This study predicts the potential mechanism of hydrochloride raloxifene in the treatment of postmenopausal osteoporosis, and provides theoretical basis and research direction for subsequent experimental research.