基于生物信息学与网络药理学探究葛根素治疗股骨头坏死的分子机制  

Molecular Mechanism of Puerarin in Treatment of Femoral Head Necrosis Based on Bioinformatics and Network Pharmacology

作　　者：骆帝 梁学振 刘金豹 许波 李刚[1,2] LUO Di;LIANG Xuezhen;LIU Jinbao;XU Bo;LI Gang(The First Clinical Medical School,Shandong University of Traditional Chinese Medicine,Jinan 250355,Shandong,China;Orthopaedic Microsurgery,Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250014,Shandong,China)

机构地区：[1]山东中医药大学第一临床医学院,山东济南250355 [2]山东中医药大学附属医院显微骨科,山东济南250014

出　　处：《中华中医药学刊》2020年第11期171-176,I0041,I0042,共8页Chinese Archives of Traditional Chinese Medicine

基　　金：国家自然科学基金(81774333,81373660);山东省重点研发计划(2016GSF202022)。

摘　　要：目的基于生物信息学和网络药理学初步分析葛根素治疗股骨头坏死的关键分子机制,为股骨头坏死的治疗提供新的研究方向与靶点。方法葛根素是中药葛根主要的提取物成分,是一种植物性雌激素。通过中药系统药理学数据库及分析平台(TCMSP)数据库、物质和化合物数据库(PubChem)以及药物靶标的蛋白质数据库(Binding DB)分析葛根素的相关作用靶点,再结合基因表达数据库(GEO)公共数据库中关于葛根素的相关芯片,借助R语言分析得到差异基因;同时检索治疗靶点数据库(TTD)等10个疾病数据库获得股骨头坏死相关疾病靶点,明确葛根素治疗股骨头坏死的关键基因,由此获得关键靶点。利用STRING数据库构建关键靶点的蛋白质-蛋白质相互作用关系;并利用DAVID数据库对关键基因进行GO分析和KEGG通路分析。结果 (1)通过检索TCMSP、PubChem、Binding DB三个数据库共获得葛根素相关靶点61个;检索GEO数据库确定葛根素相关序列号为GSE85871的芯片,利用R语言分析筛选出311个差异基因;(2)检索TTD等10个数据库共获得股骨头坏死相关疾病靶点135个;(3)利用STRING数据库构建14个关键靶点的蛋白质-蛋白质相互作用关系网络图;(4)通过DAVID在线分析功能富集显示,葛根素治疗股骨头坏死的生物学进程主要涵盖内皮细胞增殖的调节、血管的生成、一氧化氮的生物合成、序列特异性DNA结合转录因子活性的调节、蛋白质磷酸化的调节等,信号通路主要表现为低氧诱导因子1信号通路、雌激素信号通路、血管内皮生长因子信号通路及肿瘤坏死因子信号通路等。结论利用生物信息学和网络药理学能有效地分析GEO数据库的原始基因芯片数据,通过芯片内在的生物学信息分析不仅能识别目前已知的葛根素治疗股骨头坏死相关生物进程和信号通路,还能发现一些新的通路或生物学过程,为进一步深入探究其分子Objective To analyze the key molecular mechanism of puerarin in the treatment of femoral head necrosis based on bioinformatics and network pharmacologyandprovide new research directions and targets for the treatment of femoral head necrosis. Methods Puerarin is a plant estrogen, which is the main extract of Gegen(Pueraria lobata). Puerarin-related targets were analyzed by TCMSP database, PubChem database and Binding DB database of drug targets, and then differentially expressed genes were obtained by R-language analysis combined with related chips of puerarin in GEO public database. Ten disease databases, such as TTD, were used to obtain the disease targets related to femoral head necrosis and identify the key genes of puerarin in the treatment of femoral head necrosis. STRING database was used to construct the protein-protein interaction relationship of key targets, and DAVID database was used to analyze GO and KEGG pathways of key genes. Results(1) A total of 61 puerarin-related targets were obtained by searching TCMSP, PubChem and Binding DB databases. The chip GSE85871 was identified by searching GEO database, 311 differentially expressed genes were screened by R language analysis.(2) A total of 135 targets were obtained by searching 10 databases such as TTD.(3)The protein-protein interaction network map of 14 key targets were constructed by using STRING database.(4)DAVID online analysis showed that the biological process of puerarin in the treatment of femoral head necrosis mainly covered the regulation of endothelial cell proliferation, angiogenesis, nitric oxide biosynthesis, sequence-specific DNA binding transcription factor activity, protein phosphorylation regulation, and so on. And the main signal pathway included hypoxia-inducible factor-1 signaling pathway, estrogen signaling pathway, vascular endothelial growth factor signaling pathway and tumor necrosis factor signaling pathway, etc. Conclusion Bioinformatics and network pharmacology can effectively analyze the original gene chip data of GEO databa

关 键 词：葛根素 股骨头坏死 生物信息学 网络药理学 GEO数据库 

分 类 号：R274.9[医药卫生—中西医结合]