摘要
目的:利用GEO数据库及网络药理学方法研究杜仲健骨丸治疗股骨头坏死(ONFH)的作用机制。方法:ONFH疾病靶点通过GEO数据库筛选以及DrugBank、PharmGKB、GAD、OMIM、DisGeNET、GeneCards、CTD、KEGG等数据库检索获取;杜仲健骨丸的化学成分通过TCMSP和BATMAN-TCM数据库获取,并以口服生物利用度(OB)≥30%、类药性(DL)≥0.18为标准筛选有效成分,通过检索TCMSP数据库并结合经Swiss Target Prediction数据库预测的靶点作为有效成分作用靶点,将药物靶点与疾病靶点取交集,通过Cytoscape软件构建“药物-有效成分-靶点”调控网络并进行蛋白互作网络(PPI)构建及拓扑分析,利用R软件进行GO和KEGG富集分析。结果:杜仲健骨丸中主要有槲皮素、山柰酚、黄芩素、木犀草素和异鼠李素等200个有效成分,对应的靶基因1038个;GEO数据库中筛选共得到差异基因7375个,各疾病数据库获得疾病相关靶点1140个;PPI核心网络共包含AKT1、TP53、TNF和IL6等94个蛋白;GO和KEGG富集分析表明杜仲健骨丸可通过调节RNA聚合酶Ⅱ特异性转录因子结合、蛋白丝氨酸/苏氨酸激酶活性、磷酸酶结合和激素受体结合等分子功能,参与化学应激反应、氧化应激反应、活性氧反应和多肽磷酸化等生物学过程,影响膜筏、膜微区、膜区和转录调节复合体等细胞组成,作用于AGE-RAGE、PI3K-Akt、脂质和动脉粥样硬化通路、HIF-1、VEGF、FoxO和MAPK等信号通达到治疗ONFH的目的。结论:研究揭示杜仲健骨丸治疗ONFH的主要药效成分、作用靶点及相关机制,丰富其临床与实验应用的理论基础。
Objective:To explore the mechanism of Duzhong Jiangu Pill in the treatment of osteonecrosis of the femoral head(ONFH) by GEO differential gene analysis and network pharmacology.Methods:Disease targets are obtained through GEO database screening and database retrieval such as DrugBank, PharmGKB,GAD,OMIM,DisGeNET,GeneCards, CTD,KEGG,etc.The chemical components of Duzhong Jiangu Pill were searched by TCMSP and BATMAN-TCM database, the active components were screened according to the standard of oral bioavailability(OB)≥30% and drug likeness(DL)≥0.18.By searching the TCMSP database and combining the target predicted by the Swiss Target Prediction database as the active components target.The active components target and disease targets were intersected, the “drug-compound-Target” regulatory network was constructed by Cytoscape 3.7.0 software, the PPI network was constructed and topological analysis was carried out, and the enrichment analysis of gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) was carried out by using R software.Results:There were 200 effective components in Duzhong Jiangu Pill(such as quercetin, kaempferol, baicalein, luteolin, lsorhamnetin etc.) and 1 038 corresponding targets.A total of 7 375 differential genes were screened and 1 140 disease targets.There were 94 proteins in PPI core network, including AKT1,TP53,TNF,IL6 and so on.GO enrichment analysis was mainly concentrated in biological processes such as response to chemical stress, response to oxidative stress, response to reactive oxygen species, phosphorylation.KEGG analysis mainly involved AGE-RAGE signaling pathway in diabetic complications, PI3 K-Akt signaling pathway, Lipid and atherosclerosis, HIF-1 signaling pathway, VEGF signaling pathway, FoxO signaling pathway, MAPK signaling pathway and so on.Conclusion:The study provided potential molecular target and mechanism of Duzhong Jiangu Pill in the treatment of ONFH and enriches the theoretical basis of its clinical and experimental application.
作者
邹福贤
蔡建峰
黄秋萍
周晓兰
谢庆华
温秀萍
Zou Fuxian;Cai Jianfeng;Huang Qiuping;Zhou Xiaolan;Xie Qinghua;Wen Xiuping(Quanzhou Orthopedic Traumatological Hospital of Fujian University of Traditional Chinese Medicine,Quanzhou 362000,China;School of Pharmacy,Fujian University of Traditional Chinese Medicine,Fuzhou 350000,China)
出处
《亚太传统医药》
2023年第1期142-150,共9页
Asia-Pacific Traditional Medicine
基金
医疗服务与保障能力提升补助资金(中医药事业传承与发展部分)“全国中药资源普查项目”(财社[2019]39号)
福建省科技厅引导性项目(2018Y0049)
福建省教育厅省属高校科研专项资助(JK2017024)。
关键词
杜仲健骨丸
GEO
网络药理
股骨头坏死
作用机制
Duzhong Jiangu Pill
GEO
Network Pharmacology
Osteonecrosis of the Femoral Head
Mechanism
