基于网络药理学探讨药对“金银花-黄芪”对COVID-19的潜在作用机制研究

目的:运用网络药理学的方法探讨药对“金银花-黄芪”抗COVID-19的潜在机理。方法:利用中药系统药理学数据库(TCMSP)平台和BATMAN-TCM平台检索金银花、黄芪的活性化合物,并通过该数据库筛选出与活性成分相关的作用靶点;通过OMIM、GeneCards数据库筛选出与COVID-19相关的靶点。利用Cytoscape软件构建“药物-成分-疾病-靶点”网络图,并运用STRING数据库构建靶点蛋白互作PPI网络图。利用DAVID数据库对药物-疾病交集的靶点进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析。结果:筛选后得到金银花有效成分23个,黄芪有效成分20个,药物与疾病交集的靶点共10个,主要涉及NOS3、DPP4、TN、FIL6等。利用DAVID数据库分析,以P<0.05为筛选标准,得到生物过程85条,其中前20条涉及对抗生素的反应(response to antibiotic)、脂多糖介导的信号通路(lipopolysaccharide-mediated signaling pathway)、细胞增殖的负调控(negative regulation of cell proliferation)等;同时筛选得到26条信号通路,其中前20条与疟疾(Malaria)、单纯疱疹感染(Herpes simplex infection)、肿瘤坏死因子信号途径(TNF signaling pathway)等信号通路相关。结论:金银花-黄芪治疗COVID-19可能具有多成分、多靶点、多通路的特点,其作用机理可能是通过抗病毒感染和修复肺部损伤来治疗COVID-19,这为中药金银花-黄芪在临床中治疗COVID-19提供了理论依据。

Potential Targets and Molecular Mechanism of Quercetin Against Knee Osteoarthritis

Objective The objective of this study was to clarify the potential mechanism of quercetin against knee osteoarthritis(KOA)based on network pharmacology and molecular docking.Methods The targets of quercetin were predicted by PubChem and Swiss Target Prediction databases,and the targets of KOA were obtained by DisGeNET,OMIM,and GeneCards databases.Then,the targets of quercetin and KOA were intersected to find the potential targets of quercetin against KOA.The protein–protein interaction network was constructed through the STRING database,and the core targets were screened.Gene ontology(GO)functions enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed using DAVID database.The drug–target–pathway–disease network was constructed by Cytoscape software,and the molecular docking verification was performed by Vina.Results There were 49 potential targets for quercetin against KOA,including 10 core targets.GO functions enrichment analysis showed that the biological process of quercetin against KOA mainly involved the negative regulation of apoptotic process,collagen catabolic process,and extracellular matrix disassembly.KEGG pathway enrichment analysis showed that quercetin against KOA was closely related to PI3K-Akt signaling pathway,Rap 1 signaling pathway,FoxO signaling pathway,Ras signaling pathway,TNF signaling pathway,and ErbB signaling pathway.The results of molecular docking showed that the binding energies between ligand and receptors were less than−5 kcal·mol−1.Conclusions The molecular mechanism of quercetin against KOA involves many targets and pathways,which can regulate the proliferation and apoptosis of chondrocytes,degradation of extracellular matrix,and inflammatory reaction.Quercetin can stably bind to the active pockets of core target proteins,thereby exerting the effect against KOA.

城镇化对武汉市极端降水过程的影响研究——以“7.23”暴雨为例

利用天气研究与预报模式3.6版(weather research and forecasting model 3.6,WRF3.6)耦合单层城市冠层模式对武汉市2015年7月23日极端降水事件(简称“7.23”暴雨)进行了模拟研究,分析了武汉城镇下垫面扩张对暴雨过程的影响并探究其潜在机理。对比2001年和2015年武汉地区不同程度城镇化下垫面条件的模拟结果,发现城镇化改变并加剧了武汉市暴雨进程,导致暴雨范围和暴雨中心降雨量增大,暴雨持续时间缩短。在城镇面积增长了约81%的条件下,武汉市“7.23”极端暴雨24 h累积降水大于50 mm的区域增加了503.2 km^(2),特大暴雨事件面积在高城镇化条件下增长了81.8 km^(2),暴雨时长缩短了约1 h。城镇化水平显著提高后,反映低层大气稳定状况的K指数偏大,整个武汉地区更易发生极端暴雨事件;影响暴雨的最大不稳定能量范围扩大,消耗更加迅速,低层大气温度的升高也为对流运动提供了充足的热力条件,导致城市上方对流运动更加剧烈,缩短了暴雨持续时间的同时加剧了整场暴雨事件的强度。