网络药理学和生物信息学方法在骨碎补治疗股骨头坏死分子机制研究中的应用

摘要

目的 采用网络药理学和生物信息学的方法研究骨碎补治疗股骨头坏死可能的分子机制.方法 通过中药系统药理学数据库和分析平台对骨碎补可能的入血活性成分和靶点进行筛选和预测,针对TTD、DrugBank、OMIM、GAD、PharmGKB等数据库对股骨头坏死相关的作用靶点进行挖掘.结合生物信息学方法,使用BisoGenet插件对上述获得的入血活性成分及股骨头坏死相关靶点进行蛋白质-蛋白质相互关系网络绘制,利用Cytoscape软件筛选出骨碎补治疗股骨头坏死的关键靶点.采用Pathway信号通路进行富集分析,以进一步分析其可能的分子机制.结果 在中药系统药理学数据库和分析平台中共检索出与骨碎补相关的入血活性成分72个,根据药物口服生物利用度和药物相似性参数筛选获得入血活性成分18个,利用相关靶点预测技术预测可能的靶点共92个;疾病靶点相关数据库共检索到与股骨头坏死发生、发展密切相关的已知靶点72个.Cytoscape软件筛选出骨碎补治疗股骨头坏死的关键靶点92个;Pathway信号通路富集分析显示,骨碎补治疗股骨头坏死的关键靶点涉及的信号通路主要富集于细胞周期、炎症、癌症相关等35条信号通路.结论 骨碎补治疗股骨头坏死具有多成分、多靶点的特点;其主要通路不仅直接参与骨细胞的增殖、凋亡及分化,调节成骨、破骨代谢平衡,还通过调节免疫、炎症反应等干预和影响骨微环境,以达到控制股骨头坏死发生、发展的目的.%Objective To study the potential molecular mechanism of rhizoma drynariae in the treatment of osteone-crosis of the femeral head(ONFH)based on network pharmacology and bioinformatics.Methods The possible active components and targets corresponding of rhizoma drynariae were screened and predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,and the targets related to ONFH were excavated in the database of TTD,DrugBank,OMIM,GAD,PharmGKB and so on.Combined with bioinformatics method,the protein-protein interre-lation network was drew by using BisoGenet plug-in on the above-mentioned blood-intake active ingredients and ONFH-re-lated targets.Cytoscape software was used to screen out the key targets for the treatment of ONFH.The Pathway signal pathway was used to further analyze the possible molecular mechanism.Results Seventy-two corresponding compounds were retrieved in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform from Rhizoma Drynariae.According to the values of OB and DL, a total of 18 blood absorbed bioactive compounds were screened out, which obtained from the possible 92 targets by using the related target prediction technique.A total of 72 known targets closely related to the occurrence and development of ONFH were retrieved in the disease -related database.Cytoscape soft-ware screened out 92 key targets for the treatment of ONFH.The enrichment analysis of Pathway signal pathway showed that the signal pathways involved in the key targets of rhizoma drynariae in the treatment of ONFH was mainly concentrated in the cell cycle,inflammation,cancer,etc-related 35 signal pathways.Conclusions The treatment of femoral head necrosis is characterized by multi-component and multi-target by using rhizoma drynariae.Its main pathways not only directly partic-ipate in the proliferation,apoptosis and differentiation of osteocytes,regulate the bone-breaking metabolism,but also influ-ence the bone microenvironment by regulating the immune and inflammatory responses,so as to achieve the purpose of con-trolling the occurrence and development of the disease.