摘要
目的基于网络药理学和分子对接方法探究红景天防治急性高原病的作用机制。方法通过TCMID和ETCM数据库检索红景天的化学成分,再经过SwissTarget和STITCH数据库筛选红景天成分作用靶点;通过DisGeNET、Genecards及GEO数据库筛选急性高原病相关靶点;利用STRING数据库获取蛋白质相互作用(Protein-protein interaction,PPI)网络;利用DAVID数据库进行基因本体(Gene ontology,GO)功能富集分析及京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析;采用Cytoscape软件构建“药物-成分-靶点-疾病”网络及“成分-靶点-通路”网络;利用Autodock软件进行分子对接研究;采用2018年国际路易斯湖评分系统对患者症状进行评分;使用ELISA试剂盒对患者血清IL6、IL10及HIF1A水平进行测定。结果从红景天中筛选得到31个化学成分和2295个作用靶点,与1083个急性高原病相关靶点取交集,得到125个共同靶点,PPI网络中心主要涉及IL6、VEGFA、CAT、IL10、IL2、HIF1A等关键靶蛋白。KEGG富集分析主要涉及HIF-1信号通路、PI3K-AKT信号通路、VEGF信号通路等相关通路。分子对接验证显示红景天成分槲皮素、山奈酚、没食子酸、咖啡酸、红景天苷与关键靶点IL6、VEGFA、CAT、IL2、HIF1A的结合活性较好。此外,急性高原病患者在服用红景天胶囊后头痛、胃肠道症状、疲乏以及头晕情况明显缓解,症状总评分显著降低;血清中IL6和HIF1A水平显著降低,IL10水平显著升高。结论红景天能够通过多成分、多靶点、多通路的方式,发挥防治急性高原病的作用。
Objective To explore the mechanism of Rhodiola rosea on preventing and treating acute mountain sickness based on network pharmacology and molecular docking.Methods Chemical ingredients of Rhodiola rosea were obtained from TCMID and ETCM databases and potential targets of these ingredients were searched by SwissTarget and STITCH databases.Targets related to acute mountain sickness were screened through DisGeNET,Genecards and GEO databases.The STRING database was used to construct protein-protein interaction(PPI) network and the DAVID database was utilized to perform Gene ontology(GO) function and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis.The "drug-ingredient-target-disease" network and "ingredient-target-pathway" network were constructed with Cytoscape software.Molecular docking was conducted by Autodock tools.The symptoms of patients were evaluated via The 2018 Lake Louise Acute Mountain Sickness Score.The levels of serum IL6,IL10 and HIF1A were detected by ELISA kits.Results A total of 31 chemical ingredients and 2295 potential targets were obtained from Rhodiola rosea,1083 targets related to acute mountain sickness were obtained,and 125 common targets of Rhodiola rosea against acute mountain sickness were obtained.The PPI network was constructed and core targets included IL6,VEGFA,CAT,IL10,IL2,HIF1A and etc.The results of KEGG pathway enrichment analysis mainly involved HIF-1,PI3K-AKT and VEGF signaling pathways.Molecular docking suggested that quercetin,kaempferol,gallic acid,caffeic acid and salidroside have good binding capability with IL6,VEGFA,CAT,IL2 and HIF1A.In addition,headache,gastrointestinal symptoms,fatigue and dizziness were relieved by Rhodiola capsule,and the total score of symptoms was reduced.The levels of serum IL6 and HIF1A in patients with acute altitude sickness were downregulated after taking Rhodiola capsule,while IL10 was upregulated.Conclusion Rhodiola rosea might prevent and treat acute mountain sickness through a multi-ingredient,multi-target and multi-pathway action mode.
作者
司亚晨
刘冬梅
闫小荣
潘芳
Si Yachen;Liu Dongmei;Yan Xiaorong;Pan Fang(No.944 Hospital of Joint Logistics Support Force,Jiuquan 735000,China;No.940 Hospital of Joint Logistics Support Force,Lanzhou 730050,China;Jiuquan Hospital of Traditional Chinese Medicine,Jiuquan735000,China)
出处
《世界科学技术-中医药现代化》
CSCD
北大核心
2023年第1期144-155,共12页
Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology
基金
联勤保障部队第九四〇医院2020-2021年度院内科研计划项目(2021yxky011):基于多组学联合分析的重症急性高原病早期生物标志物筛选及相关机制研究,负责人:刘冬梅
联勤保障部队第九四〇医院2021-2022年度院内科研计划项目(2022yxky014):高原肺水肿早期预警和精准识别研究,负责人:刘冬梅。
关键词
红景天
急性高原病
网络药理学
分子对接
Rhodiola rosea L.
Acute mountain sickness
Network pharmacology
Molecular docking
作者简介
通讯作者:刘冬梅,副教授,主要研究方向:重症医学及急性高原病防治;通讯作者:潘芳,副主任医师,主要研究方向:中西医结合治疗内科疾病。
