摘要
目的:基于生物信息学及计算机模拟对复方大蓟饮子治疗上消化道出血的机制进行探究。方法:通过中药系统药理学数据库与分析平台(TCMSP)与中医药整合药理学研究平台(TCMIP)查找大蓟饮子的药物成分及靶点,在Swiss Target Prediction平台对靶点较少的成分进行靶点预测,运用GeneCards、DisGeNET、TTD、OMIM数据库对上消化道出血的靶点进行搜集,通过韦恩图获取药物与疾病交集靶点后,在STRING数据库构建蛋白质–蛋白质相互作用网络,通过DAVID数据库进行核心靶点的功能与通路富集分析,使用AutoDock Vina进行半柔性分子对接验证,通过分子动力学模拟对结合较好的结果进行深入验证。结果:筛选得到大蓟饮子活性成分27种,对应靶点231个,上消化道出血靶点5597个,二者的交集靶点183个,经蛋白质–蛋白质相互作用网络分析确定槲皮素、刺槐黄素及豆甾醇等核心成分与丝氨酸/苏氨酸蛋白激酶1(Akt Serine/Threonine Kinase 1,AKT1)、肿瘤坏死因子(Tumor Necrosis Factor,TNF)及白细胞介素(Interleukin,IL)-6等关键靶点存在显著关联,通路富集主要涉及癌症相关通路、脂质与动脉粥样硬化、磷脂酰肌醇3激酶(Phosphatidylinositol 3 Kinase,PI3K)–蛋白激酶B(Akt)信号通路与晚期糖基化终末产物–晚期糖基化终末产物受体(Advanced Glycation End Product-Receptor for Advanced Glycation End Products,AGE-RAGE)等信号通路,分子对接及分子动力学模拟结果验证了药物核心成分与关键靶点间的稳定结合。结论:大蓟饮子可通过激活AGE-RAGE通路、抑制PI3K-Akt和TNF等信号通路从而激活凝血因子的表达、促进血管收缩及血小板凝聚、加速受损细胞修复等发挥上消化道出血治疗作用,可为上消化道出血的临床治疗提供全新的理论依据。
Objective:To explore the mechanism of the Daji Yinzi decoction(复方大蓟饮子)in the treatment of upper gastrointestinal bleeding(UGIB)based on bioinformatics and computer simulation.Methods:The chemical components and targets of the Daji Yinzi decoction were searched through TCMSP and TCMIP.For components with fewer targets,target prediction was performed using the Swiss Target Prediction platform.The targets of UGIB were collected from the GeneCards,DisGeNET,TTD,and OMIM databases.After obtaining the intersection targets via the Venn diagram,a protein-protein interaction(PPI)network was constructed in the STRING database.Functional and pathway enrichment analyses of the core targets were conducted through the DAVID database.Semi-flexible molecular docking verification was carried out using AutoDock Vina,and in-depth verification of the results with better binding was performed through molecular dynamics simulation.Results:After screening,27 active components of the Daji Yinzi decoction were obtained,corresponding to 231 targets,and 5597 targets of UGIB were identified.The Venn diagram revealed 183 intersecting targets of the two.Through PPI analysis,it was determined that core components such as quercetin,acacetin,and stigmasterol had significant associations with key targets including AKT1,TNF,and IL-6.Pathway enrichment mainly involved cancer-related pathways,lipid and atherosclerosis,PI3K-Akt signaling pathway,and AGE-RAGE signaling pathway in diabetic complications.The results of molecular docking and molecular dynamics simulation confirmed the stable binding between the core components of the drug and the key targets.Conclusion:The Daji Yinzi decoction exerts its therapeutic effects on UGIB by activating the AGE-RAGE pathway,inhibiting signaling pathways such as PI3K-Akt and TNF,thereby activating the expression of coagulation factors,promoting vasoconstriction and platelet aggregation,and accelerating the repair of damaged cells.These findings can provide novel theoretical basis for the clinical treatment of UGIB.
出处
《中医临床研究》
2025年第23期1-11,共11页
Clinical Journal Of Chinese Medicine
基金
国家中医药管理局民族药学三级实验室项目(PTZ24024)。
关键词
大蓟饮子
上消化道出血
生物信息学
分子对接
分子动力学模拟
The Daji Yinzi decoction
Upper gastrointestinal bleeding
Network pharmacology
Molecular docking
Molecular dynamics simulation
