基于网络药理学研究杜仲抗骨质疏松的分子机制
投稿时间:2018-02-27     点此下载全文
引用本文:李嘉程,许波,李刚,阎博昭,夏聪敏,梁学振,骆帝.基于网络药理学研究杜仲抗骨质疏松的分子机制[J].中国现代中药,2018,20(8):936-942
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作者中文名作者英文名单位中文名单位英文名E-Mail
李嘉程 LI Jia-cheng 山东中医药大学 第一临床医学院,山东济南250355 Shandong University of Traditional Chinese Medicine,the First Clinical Medical College,Jinan 250355,China  
许波 XU Bo 山东中医药大学 附属医院 显微骨科,山东济南250355 Shandong University of Traditional Chinese Medicine,Jinan 250355,China  
李刚 LI Gang 山东中医药大学 附属医院 显微骨科,山东济南250355 Shandong University of Traditional Chinese Medicine,Jinan 250355,China 李刚,博士,教授,博士生导师,研究方向:骨与关节疾病;E-mail:doctorlee808@163.com 
阎博昭 YAN Bo-zhao 山东中医药大学 第一临床医学院,山东济南250355 Shandong University of Traditional Chinese Medicine,the First Clinical Medical College,Jinan 250355,China  
夏聪敏 XIA Cong-min 山东中医药大学 中医学院,山东济南250355 Shandong University of Traditional Chinese Medicine,the College of Traditional Chinese Medicine,Jinan 250355,China  
梁学振 LIANG Xue-zhen 山东中医药大学 第一临床医学院,山东济南250355 Shandong University of Traditional Chinese Medicine,the First Clinical Medical College,Jinan 250355,China  
骆帝 LUO Di 山东中医药大学 第一临床医学院,山东济南250355 Shandong University of Traditional Chinese Medicine,the First Clinical Medical College,Jinan 250355,China  
基金项目:山东省自然科学基金项目(ZR2017LH067)
中文摘要:目的:基于网络药理学探究杜仲抗骨质疏松可能的分子机制。方法:采用活性成分筛选、靶点预测技术,结合生物信息学手段,预测杜仲防治骨质疏松症的作用靶点,并进行信号通路富集分析,从而探讨其治疗骨质疏松症的分子机制。结果:杜仲在TCMSP数据库中共检索到94个相应成分,根据口服生物利用度(oral bioavailability,OB)和药物相似性(drug-likeness,DL)参数共筛选到25个入血活性成分,同时利用相关靶点预测技术,共获得101个预测靶点。通过对GEO芯片数据库的基因芯片进行二次挖掘分析,共获取124个明显的差异基因;在疾病基因相关数据库共检索到356个与骨质疏松症发生、发展密切相关的已知靶点基因。利用cytoscape构建并合并活性成分及疾病的蛋白质相互作用关系网络,通过网络拓扑分析共筛选出232个关键基因;ClueGO富集分析显示,杜仲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、NF-kappa B信号通路、FoxO信号通路等有关,还对P13K-Akt信号通路、GnRH信号通路、甲状腺素信号通路、雌激素信号通路等同时进行调控。结论:杜仲治疗骨质疏松症具有多成分、多靶点的特点;其主要通路不仅可能直接参与骨重建的细胞分化,调节成骨、破骨代谢平衡,还可能通过全身其他系统,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。
中文关键词:杜仲  骨质疏松症  网络药理学  生物信息学  分子机制  信号通路
 
Study on Molecular Mechanism of Osteoporosis Treated by Eucommia ulmoides Based on Network Pharmacology
Abstract:Objective:To clarify the molecular mechanism of Eucommia ulmoides in the treatment of osteoporosis.Methods:The method of network pharmacology was used to determine and screen the known compounds corresponding to E.ulmoides,and predict the drug-related gene/protein targets,and combined with bioinformatics,the specific target of osteoporosis prevention and treatment of E.ulmoides was determined,and then through the analysis of the signal pathway enrichment,the molecular mechanism of E.ulmoides in treatment of osteoporosis was further analyzed.Results:94 corresponding compounds were retrieve in the TCMID database from E.ulmoides.According to the values of OB and DL,a total of 25 blood transfusion components were screened,which obtained 101 targets by using the related target prediction technique.Through the secondary mining of the genechip of GEO chip database,we obtained a total of 124 significantly different genes.And a total of 356 known target genes closely related to the development of osteoporosis were retrieved in the disease-related database.Using the cytoscape to construct and synthesize the protein-protein interaction network of active ingredients and diseases,232 key genes were screened out by network to pological analysis.Using ClueGO analysis,it is shown that E.ulmoides is directly involved in the signal pathways involved in the key nodes of osteoporosis,which are mainly related to the direct regulation of bone metabolism,such as Estrogen signaling pathway Wnt signaling pathway,HIF-1 signaling pathway,MAPK signaling pathway,PI3K-Akt signaling pathway,FoxO signaling pathway,NF-kappa B signaling pathway,neurotrophin signaling pathway,prolactin signaling pathway and neurotrophin signaling pathway.Conclusion:E.ulmoides has the character of multiple targets and multicomponent in the treatment of osteoporosis,which could involve not only directly in bone cell differentiation and regulation of the balance of ontogenesis and osteoclasts,but also affect and interfere with the bone micro environment through other systemic systems,such as circulatory system,nervous system,which is consistent with the current mechanism of treatment of osteoporosis.
keywords:Eucommia ulmoides  osteoporosis  network pharmacology  bioinformatics  molecular mechanisms  signaling pathway
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