基于网络药理学和分子对接技术预测昆明山海棠治疗口腔扁平苔藓的潜在靶点和分子机制

目的:联合采用网络药理学和分子对接技术,探究昆明山海棠治疗口腔扁平苔藓(oral lichen planus,OLP)的潜在靶点和分子机制。方法:筛选昆明山海棠有效成分及靶点,预测OLP相关靶点,构建昆明山海棠和OLP交集靶点的蛋白质相互作用(protein-protein interaction,PPI)网络,建立“OLP-靶点-分子-昆明山海棠”网络并进行可视化分析,筛选出的交集基因进行基因本体论(gene ontology,GO)功能分析和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,分子对接分析及可视化。结果:获得昆明山海棠有效成分15个,靶点78个,筛选得到与OLP相关靶点9109个,昆明山海棠与OLP交集基因54个,从构建的PPI网络筛选获得前10个核心靶点,从构建的“OLP-作用靶点-有效成分-昆明山海棠”网络筛选获得昆明山海棠前10个有效成分,对54个交集靶点的GO分析和KEGG分析结果表明,昆明山海棠可能通过调节一碳叶酸循环、肿瘤信号通路等途径发挥治疗作用,分子对接分析结果表明,二氢叶酸还原酶(dihydrofolate reductase,DHFR)、磷酸核糖甘氨酰胺转甲酰酶(phosphoribosylglycinamide formyltransferase,GART)、雌激素受体1(estrogen receptor 1,ESR1)等是昆明山海棠治疗OLP的关键靶点。结论:本研究获得昆明山海棠治疗OLP的潜在靶点及分子机制,为促进靶向药物的研发及临床应用提供理论基础。

Prediction of potential targets and molecular mechanisms of Tripterygium hypoglaucum for oral lichen planus based on network pharmacology and molecular docking

Objective:To explore the potential targets and molecular mechanisms of tripterygium hypoglaucum for oral lichen planus(OLP)by applying network pharmacology and molecular docking technology.Methods:The active ingredients and targets of tripterygium hypoglaucum were screened.OLP-related targets were predicted.The Protein-Protein Interaction(PPI)network was constructed for the intersection targets of tripterygium hypoglaucum and OLP.The“OLP-target-molecule-Tripterygium hypoglaucum”network was constructed and visualized.The intersection genes were screened for gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses.Molecular docking analysis and visualization were performed.Results:15 active ingredients and 78 targets of tripterygium hypoglaucum were obtained.9109 OLP-related targets were screened,and 54 intersection genes of tripterygium hypoglaucum with OLP were obtained.The top 10 key targets were screened from the constructed PPI network.The top 10 active ingredients of tripterygium hypoglaucum were screened from the constructed“OLP-targets of actionactive ingredients-tripterygium hypoglaucum”network.The GO and KEGG analyses of the 54 intersection targets indicated that tripterygium hypoglaucum may play a therapeutic role by regulating one carbon pool by folate,pathways in cancer,et al.Molecular docking analysis showed that dihydrofolate reductase(DHFR),phosphoribosylglycinamide formyltransferase(GART),estrogen receptor 1(ESR1),et al are the key targets for the treatment of OLP in tripterygium hypoglaucum.Conclusion:The potential key targets and molecular mechanisms of tripterygium hypoglaucum in treating OLP provide a theoretical basis for new drug development and clinical applications.

基于代谢组学探讨血府逐瘀汤对冠心病心血瘀阻证模型大鼠的疗效机制

研究血府逐瘀汤对冠心病心血瘀阻证模型大鼠心肌代谢产物的影响,探讨活血化瘀法疗效机制。SD大鼠随机分为假手术组、模型组、血府逐瘀汤组(14.04 g·kg^(-1))、曲美他嗪组(5.4 mg·kg^(-1)),假手术组只穿线不结扎,其余组通过冠状动脉左前降支结扎法制备冠心病心血瘀阻证模型,造模3 d后进行药物干预,干预14 d后取材。观察一般状态,检测心电图、心脏彩超指标,苏木精-伊红(hematoxylin-eosin,HE)染色、Masson染色观察组织病理形态学,酶联免疫吸附测定法(enzyme linked immunosorbent assay,ELISA)检测血清甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC)含量,利用超高效液相色谱-质谱联用(ultra high performance liquid chromatography-quantitative exactive-mass spectrometry,UHPLC-QE-MS)技术筛选心肌组织差异代谢物,并进行代谢通路富集分析。结果表明,血府逐瘀汤可以显著改善模型大鼠的一般状态,降低心电图心率、ST段抬高幅度,升高左室射血分数(left ventricular ejection fraction,LVEF)和短轴缩短率(left ventricular fractional shortening,LVFS),降低左室舒张末内径(left ventricular intemal diameter in diastole,LVIDd)和左室收缩末内径(left ventricular intemal diameter in systole,LVIDs);HE染色与Masson染色显示,血府逐瘀汤可有效减轻模型大鼠的心肌组织结构紊乱、炎性细胞浸润与胶原纤维沉积;ELISA结果显示,血府逐瘀汤有效调节模型大鼠的血清TG、TC水平。各组心肌样本的代谢表型差异明显,共鉴定出血府逐瘀汤组回调的14种差异代谢物,涉及5条代谢通路,包括精氨酸和脯氨酸代谢,甘油磷脂代谢,氨酰基tRNA生物合成,醚脂代谢,丙氨酸、天冬氨酸和谷氨酸代谢。血府逐瘀汤改善冠心病心血瘀阻证模型大鼠的心功能、心肌结构损伤,其生物学机制涉及调节脂质代谢、胆碱代谢、氨基酸代谢、能量代谢、蛋白质合成等相关途径。