基于网络药理学和分子对接探讨益肾健骨方治疗绝经后乳腺癌患者骨质疏松的机制及实验验证  

Mechanism of Yishen Jiangu Decoction in the Treatment of Postmenopausal Breast Cancer Patients with Osteoporosis Based on Network Pharmacology and Molecular Docking

作　　者：孟慧 于明薇[2] 陈宇晗[1,2] 马云飞 王笑民[2] Meng Hui;Yu Mingwei;Chen Yuhan;Ma Yunfei;Wang Xiaomin(Graduate school,Beijing University of Chinese Medicine,Beijing 100029,China;Beijing Hospital of Traditional Chinese Medicine,Capital Medical University,Beijing 100010,China)

机构地区：[1]北京中医药大学研究生院,北京100029 [2]首都医科大学附属北京中医医院,北京100010

出　　处：《世界科学技术-中医药现代化》2022年第4期1629-1641,共13页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：北京市自然科学基金委员会面上项目(7202065):益肾健骨方通过RANKL-RANK-OPG轴调控阿那曲唑相关骨丢失的机制研究,负责人:于明薇;北京市科委北京市科技计划项目(Z191100008319006):2019年北京市落实中央引导地方科技发展专项,负责人:王笑民。

摘　　要：目的 运用网络药理学和分子对接的方法研究益肾健骨方治疗绝经后乳腺癌骨质疏松症的作用机制。方法 通过中药系统药理数据库和分析平台(TCMSP)和中医综合数据库(TCMID)获取益肾健骨方的活性成分和靶点,以口服生物利用度(OB)≥30%和类药性(DL)≥0.18为阈值进行潜在活性成分筛选。通过药物靶标数据库(TTD)、药物数据库(DrugBank)、疾病相关的基因与突变位点数据库(DisGenet)数据库收集疾病靶点,筛选出与益肾健骨方的交集靶点。运用Cytoscape3.7.2构建疾病-化合物-靶点网络,蛋白相互作用网络(PPI)。采用Metascape进行基因本体(GO)功能富集分析和京都基因与基因百科全书(KEGG)通路富集分析,通过分子对接将关键靶点和潜在靶点与活性成分的相互作用进行验证。结果 益肾健骨方中共筛选到药代动力学较好的活性成分β-谷甾醇、谷甾醇、豆甾醇、槲皮苷、山柰酚等113种,得到GO富集条目(P<0.05)1048条,KEGG通路富集得到84条信号通路(P<0.05)。分子对接结果显示槲皮苷与核心靶点和潜在靶点结合稳定,涉及肿瘤通路、人乳头瘤病毒感染通路、PI3K-Akt信号通路等。大鼠体内实验验证益肾健骨方可以增加骨小梁密度及骨组织胶原溶剂比,改善大鼠骨质疏松状态。结论 益肾健骨方可能通过多靶点、多通路治疗乳腺癌绝经后骨质疏松症。Objective To study the mechanism of Yishen Jiangu Decoction in the treatment of postmenopausal breast cancer osteoporosis by using network pharmacology and molecular docking.Methods The active ingredients and targets of Yishen Jiangu Decoction were obtained through pharmacological database and analysis platform of Chinese medicine system(TCMSP) and comprehensive database of Chinese medicine(TCMID). The threshold values of oral bioavailability(OB) ≥30% and drug-like(DL) ≥0.18 were used to screen the potential active ingredients. The disease targets were collected through Drug Target Database(TTD), Drug Database(DRUGBANK) and Disease Related Genes and Mutation Site Database(DISGENET) to screen out the intersection targets of Yishen Jiangu Decoction. The disease-compoundtarget network and protein interaction network(PPI) were constructed by Cytoscape 3.7.2. Metascape was used for gene ontology(GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genes(KEGG) pathway enrichment analysis, and the interactions of key targets and potential targets with active ingredients were verified by molecular docking. Results A total of 113 active ingredients with better pharmacokinetics, such as β-sitosterol, sitosterol,stigmasterol, quercetin and kaempferol were screened in Yishen Jiangu Decoction and 1048 GO enrichment items were obtained(P<0.05), and 84 signal pathways were obtained from KEGG pathway enrichment(P<0.05). Molecular docking results showed that quercetin had stable binding with core and potential targets, involving tumor pathways, human papillomavirus infection pathways, PI3K-Akt signaling pathways. etc. Conclusion The main active components of Yishen Jiangu Decoction include β-sitosterol, sitosterol, stigmasterol, quercetin and kaempferol, etc., which can treat breast cancer postmenopausal osteoporosis through multiple targets.

关 键 词：益肾健骨方 骨质疏松 乳腺癌 网络药理学 分子对接 

分 类 号：R285[医药卫生—中药学]