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作 者:冯俊芳[1] 王一彪 陈欧 高雁翎[1] FENG Jun-fang;WANG Yi-biao;CHEN Ou;GAO Yan-ling(Department of Neonatology,Dezhou People's Hospital,Dezhou 253000,Shandong,CHINA;Department of Pediatrics,Second Hospital of Cheeloo College of Medicine,Shandong University,Dezhou 250033,Shandong,CHINA;School of Nursing,Cheeloo College of Medicine,Shandong University,Jinan 250012,Shandong,CHINA)
机构地区:[1]德州市人民医院新生儿科,山东德州253000 [2]山东大学齐鲁医学院第二医院儿科,山东济南250033 [3]山东大学齐鲁医学院护理学院,山东济南250012
出 处:《海南医学》2021年第18期2369-2374,共6页Hainan Medical Journal
摘 要:目的运用网络药理学方法研究大黄酸-靶点-通路,探讨其治疗新生儿急性呼吸窘迫综合征的抗炎作用机制。方法应用中药分子机制生物信息学分析平台获取大黄酸对应靶点,并进行分子对接。应用Cytoscape3.7.1软件构建大黄酸-预测靶点网络,并对网络拓扑结构进行分析。在TTD数据库中搜索抗炎靶点,应用STRING数据库构建PPI网络,与大黄酸-预测靶点网络融合,筛选大黄酸的抗炎靶点。建立大黄酸抗炎靶点对抗新生儿急性呼吸窘迫综合征的体内反应网络,筛选与急性呼吸窘迫综合征发病相关的抗炎靶点。应用Enrichr数据库分析大黄酸抗炎靶点的Kyoto Encyclopedia of Genes and Genomes(KEGG)信号通路。结果筛选得出大黄酸对应10个靶点蛋白,其中肿瘤坏死因子受体超家族成员1A(TNFRSF1A)、表皮生长因子受体(EGFR)、受体蛋白酪氨酸激酶(Erb-B2)及丝裂原活化蛋白激酶(MAPK14)4个靶点可能是大黄酸治疗新生儿急性呼吸窘迫综合征的重要抗炎靶点。通过PPI网络分析及KEGG通路富集分析得到大黄酸可以调控MAPK等相关信号通路,并通过体外实验验证了大黄酸抑制人支气管上皮(HBE)细胞炎症反应的分子机制。结论TNFRSF1A、EGFR、Erb-B2及MAPK14可能为大黄酸的抗炎作用靶点,大黄酸可通过调控MAPK等信号通路,控制新生儿急性呼吸窘迫综合征的发生、发展,延缓病情恶化。Objective To study rhein-target-pathway and predict its anti-inflammatory mechanism in the treat-ment of neonatal acute respiratory distress syndrome by using network pharmacology.Methods The corresponding tar-gets of rhein were obtained by using the bioinformatics analysis platform of molecular mechanism of Traditional Chi-nese medicine,and the molecular docking was carried out.Cytoscape 3.7.1 software was used to construct the rhein-tar-get network,and the topology structure of the network was analyzed.The TTD database was used to search for anti-in-flammatory targets,and PPI network was constructed by using STRING database,which was fused with the rhein-target network to screen the anti-inflammatory targets of rhein.An in vivo response network of rhein anti-inflammatory targets against neonatal acute respiratory distress syndrome(ARDS)was established to screen anti-inflammatory targets of rhe-in related to the onset of ARDS.The Enrichr database was used to analyze KEGG signaling pathway of rhein anti-inflam-matory targets.Results Ten related target proteins were screened in the relevant databases.Epidermal growth factor re-ceptor(EGFR),receptor tyrosine kinase Erb-B2,mitogen-activated protein kinase(MAPK14),and tumor necrosis factor receptor superfamily member 1A(TNFRSF1A)may be important anti-inflammatory targets for the treatment of neonatal acute respiratory distress syndrome with rhein.PPI network analysis and KEGG pathway enrichment analysis predicted that rhein could regulate MAPK and other signaling pathways.Consistently,further in vitro experiments demonstrated that rhein was shown to inhibit HBE cells inflammation.Conclusion MAPK14,EGFR,ERBB2,TNFRSF1A may be anti-inflammatory targets of rhein.MAPK and other signaling pathways can be regulated to control the occurrence and development of neonatal acute respiratory distress syndrome and delay the deterioration of the disease.
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