The Treatment Points for Osteoporosis with Different Causes and Pathogenesis Based on Bioinformatics Methods
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目的:探讨在生物信息学方法指导下骨质疏松症(osteoporosis,OP)不同病因病机的治疗要点.方法:以滋补肝肾、益气健脾、活血化瘀代表药物为搜索词,在中药系统药理数据库检索活性成分及预测靶点,借助Cytoscape 3.7.2软件构建药物与靶点之间的网络图.通过基因表达数据库(gene expression omnibus database,GEO)相关芯片分析差异基因,结合疾病数据库获取OP所有疾病靶点并构建药物与疾病的关键靶点韦恩图.通过DAVID数据库对关键靶点进行基因本体及京都基因与基因组百科全书富集,以探讨不同病因病机下OP的防治要点.结果:滋补肝肾、益气健脾及活血化瘀组分别筛选出146个、126个及117个靶点,GEO数据库筛选出1173个差异基因,疾病数据库筛选出靶点336个,去重整合后共获得OP靶点1469个.滋补肝肾、益气健脾组映射出25个相同靶点,活血化瘀组映射出21个关键靶点.基因可视化分析发现肝肾亏虚及脾胃虚弱型OP的治疗要点,且主要集中在肿瘤坏死因子通路、核苷酸结合寡聚化结构域样受体通路等方面;气血瘀阻型的治疗要点主要在血管内皮生长因子通路、缺氧诱导因子1通路等方面.结论:OP具有复杂的病因病机,在对症治疗时,肝肾亏虚及脾胃虚弱型更应注重控制体内炎症水平,气血瘀阻型更应注意体内局部血管构建及纠正缺氧状态.同时,众多病因病机之间存在着相似病理过程,也应注重全面调控及防治.
Objective:To discuss the treatment points for osteoporosis with different causes and patho-genesis based on bioinformatics methods.Methods:The representative drugs of nourishing liver and kidney,benefitting Qi and invigorating spleen,activating blood and removing stasis were chosen as the key words to search the active ingredients and the predicted targets from the traditional Chinese medicine systems pharma-cology database and analysis platform(TCMSP),to construct the network diagram between drug and targets via Cytoscape 3.7.2 software.The differential genes were analyzed via gene expression omnibus database(GEO)associated microarrays,combined with disease database,all the disease targets of osteoporosis were obtained,and venny diagram of key targets of drugs and disease was constructed.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)of the key targets were performed using DAVID databases,to discuss the treatment points of osteoporosis with different causes and pathogenesis.Results:All 146 targets,126 ones and 117 ones were screened in the groups of nourishing liver and kidney,benefitting Qi and invigorating spleen,activating blood and removing stasis respectively,1173 differential genes were screened from GEO database,336 targets were screened from disease database,after de-reintegration,all 1469 osteoporosis-related targets were gained.The groups of nourishing liver and kidney,benefitting Qi and invigorating spleen mapped 25 common targets,the group of activating blood and removing stasis mapped 21 key targets.Genetic visualization analysis showed that the main therapeutic points of osteoporosis of liver and kidney depletion pattern,spleen-stomach weakness pattern lie in tumor necrosis factor pathway,nucleotide-binding oligomerisation structural domain-like receptor pathway,etc;the main therapeutic points of osteoporosis of Qi and blood stagnation pattern mainly focus on vascular endothelial growth factor pathway and hypoxia-inducible factor-1 pathway.Conclusion:Osteoporosis has a complicated etiology and pathogenesis.In symptomatic treatment,we should pay attention to the regulation of the level of inflammation in the patients with osteoporosis of liver and kidney depletion pattern,spleen-stomach weakness pattern,and focus on the construction of local vessels and the correction of hypoxic state in the patients of Qi and blood stagnation pattern.Meanwhile we should focus on the complete regulation,the prevention and the treatment,as there are similar pathological processes among many causes and pathogenesis.
osteoporosisthe cause and pathogenesisGEO databasenetwork pharmacologyTCM and materia medica
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