摘要
目的探讨补虚与活血配伍治疗股骨头坏死(ONFH)的潜在作用机制。方法以使用频率最高的当归、熟地黄、续断、杜仲、黄芪和丹参、牛膝、红花、川芎、骨碎补为例,利用中药系统药理学分析平台数据库(TCMSP)筛选补虚药与活血药的有效成分,并收集其对应的预测靶点;采用Cytoscape 3.7.2软件进行"药物-成分-靶点"网络构建与分析;利用DisGeNET、PharmGKB、CTD、GAD、OMIM、GeneCards、KEGG等数据库检索与ONFH相关作用靶点;借助OmicShare平台筛选补虚药与活血药配伍治疗ONFH的作用靶点;采用STRING数据库进行蛋白质相互作用(PPI)网络的构建与分析,通过DAVID生物信息学资源数据库进行GO分析和KEGG通路富集分析。结果共筛选出补虚药有效成分53个、预测靶点142个,活血药有效成分118个、预测靶点148个;检索出ONFH相关作用靶点1159个,补虚药与活血药预测靶点与疾病ONFH的交集靶点有53个;PPI网络共包含节点52个、边477条,平均节点度值为18,平均介数为0.718;GO分析结果显示,交集靶点生物过程主要涉及RNA聚合酶Ⅱ启动子转录正调控等,细胞组分主要包括细胞核、细胞质等,分子功能主要包括蛋白质结合、金属离子结合等;KEGG通路富集分析结果显示,交集靶点主要与癌症通路、PI3K-Akt信号通路、肺结核、HIF-1信号通路、南美锥虫病等通路有关。结论补虚药与活血药配伍主要通过潜在的"多成分-多靶点-多通路"来发挥作用,并通过不同成分作用于相同靶点、相同通路协同起效来达到治疗ONFH的目的。
Objective To explore the potential mechanism of tonifying deficiency and activating blood circulation method in the treatment of necrosis of femoral head(ONFH).Method Using the most frequent examples of Danggui(Angelicae Sinensis Radix),Shudihuang(Rehmanniae Radix Praeparata),Xuduan(Dipsaci Radix),Duzhong(Eucommiae Cortex),Huangqi(AstragaliRadix)and Danshen(Salviae Miltiorrhizae Radix Et Rhizoma),Niuxi(Achyranthis Bidentatae Radix),Honghua(Carthami Flos),Chuanxiong(Chuanxiong Rhizoma)and Gusuibu(Drynariae Rhizoma).The active components of tonic and blood-activating drugs were selected and their corresponding predictive targets were collected by TCMSP.Cytoscape 3.7.2 software was used to constructand analyze the“drug-component-target”network.ONFH-related action targets were searched and retrievedby using DisGeNET,PharmGKB,CTD,GAD,OMIM,GeneCards,KEGG and other databases.The action targets of ONFH with the combination of tonifying drugs and activating drugs were screened byusing the Omicshare platform.The protein interaction(PPI)network was constructed and analyzed by using the string database,and GO analysis and KEGG pathway enrichment analysis werecarried out through the DAVID bioinformatics resource database.Result A total of 53 active components of tonifying drugs,142 predicted targets,118 active components of activating drugs,and 148 predicted targets were selected.A total of 1159 related targets of action of ONFH were retrieved,53 targets of intersection of anti-deficient drugs and disease ONFH were detected.PPI network consisted of 52 nodes,477 edges,18 average nodes,with an average number of 0.718.GO analysis showed that the intersection biological process mainly involved in the positive regulation of polymerase II promoter transcription and so on.The main components of the cell included nucleus,cytoplasm and other molecules,and protein binding metal ion binding.KEGG pathway enrichment analysis results showed that the intersection of the main targets was related to Pathways in cancer,PI3 K-Akt signaling pathway,Tuberculosis,HIF-1 signaling pathway,American trypanosomiasis and so on.Conclusion The compatibility of tonifyingand activating blood drugs mainly plays a role through the potential“multi-component-multi-target-multi-pathway”,and achieves the purpose of treating ONFH by acting on the same target and the same pathway synergistically by different components.
作者
盛韦菖
梁学振
许波
刘金豹
朱凯
李刚
SHENG Weichang;LIANG Xuezhen;XU Bo;LIU Jinbao;ZHU Ke;LI Gang(Shandong University of Traditional Chinese Medicine,Jinan 250355,Shandong,China;Affiliated Hospital of Shandong University of traditional Chinese Medicine,Jinan 250014,Shandong,China)
出处
《辽宁中医杂志》
CAS
2021年第7期152-156,257,共6页
Liaoning Journal of Traditional Chinese Medicine
基金
国家自然科学基金(81774333)
关键词
股骨头坏死
补虚药
活血药
网络药理学
作用机制
osteonecrosis of femeral head
tonifying deficiency drugs
activating blood drugs
network pharmacology
action mechanism
