目的:采用网络药理学方法探讨开心散治疗抑郁症和抑郁症合并心肌梗死(myocardial in-farction,MI)的主要成分、作用靶点、传导通路和作用机制的异同并对关键靶点进行实验验证.方法:基于公共数据库结合ADME算法筛选开心散有效成分和作用靶点;通过DisGeNET数据库筛选抑郁症和MI及其共病靶点;利用STRING 11.0数据库构建蛋白-蛋白互作(protein-protein interactions,PPI)网络;通过核心靶基因导入基因功能注释数据库(the database for annotation,visualization and integrated discovery,DAVID)进行京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)靶点相关通路分析;通过Cytoscape构建"药物成分-靶点-通路"网络;分析药物成分血脑屏障通过性,并采用Autodock Vina软件进行分子对接验证;建立抑郁症体外模型,采用蛋白质免疫印迹法(western blot,WB)对关键蛋白表达进行验证.结果:筛选出抑郁症与MI共同靶点28个;开心散主要成分30种,治疗抑郁症潜在靶点36个,其中关键靶点为Akt1、TNF、MAPK8、JUN、PTGS2、IL1B、IFNG、GSK3B、NOS2、DRD1等;开心散治疗抑郁症合并MI的主要成分14种,共同作用关键靶点为Akt1、TNF、IL1B、GSK3B、NOS2、BAX、NR3C2、NOS3、ESR1、ADRB1;开心散治疗抑郁症的成分较治疗抑郁症合并MI共同成分具有更强的血脑屏障通过性;分子对接结果显示山柰酚作用于Akt1靶点,参与调控PI3K/Akt通路;体外实验证实山柰酚可上调抑郁模型细胞Akt1蛋白表达.结论:开心散治疗抑郁症和抑郁症合并MI成分和靶点既有相同之处也有不同之处,体现"异病同治"的特点,且其治疗抑郁症主要侧重于对中枢神经系统和内分泌系统的调节,验证实验证实开心散对于治疗抑郁症和抑郁症合并MI具有有效性.
Pharmacological Study and Key Target Validation of the Mechanism of Difference between Kaixin San for Depression,and Depression Combined with Myocardial Infarction
Objective:To investigate the similarities and differences in the main components,targets,conduction pathways and mechanisms of action of Kaixinsan(KXS)in the treatment of depression,and depression combined with myocardial infarction(MI)using network pharmacology and to validate the key targets using the experiments.Methods:The active ingredients and the targets of KXS were screened based on public database and ADME algorithm;depression and MI,and the shared targets between the diseases were screened from DisGeNET database;protein-protein interaction was constructed using STRING 11.0;KEGG targets related pathways were analyzed using DAVID database;"component-target-pathway"network was constructed by Cytoscape;the blood-brain barrier permeability of drug components was analyzed,and"molecule-key target"docking was verified by Autodock Vina software;the cell model was established,and the expression of key proteins was verified using western blot method.Results:there were 28 co-morbid targets of depression and myocardial infarction identified;30 main components of KXS,and 36 potential targets for depression treatment,among them,the key targets including Akt1,TNF,MAPK8,JUN,PTGS2,IL1B,IFNG,GSK3B,NOS2,DRD1,etc.;14 main components of KXS involved in the treatment of depression-combined with myocardial infarction and key targets of the co-morbid disease were Akt1,TNF,IL1B,GSK3B,NOS2,BAX,NR3C2,NOS3,ESR1,ADRB1;the components of KXS for the treatment of depression have stronger blood-brain barrier passage than those for the treatment of depression and MI;molecular docking predicts that kaempferol can potentially initiate Akt1 targets and participate in the regulation of PI3K/Akt1 pathway;experiments have confirmed that the ingredient could up-regulate cellular expressions of Akt1 in depression model.Conclusion:KXS has both the same and different components and targets in the treatment of depression,and depression combined with myocardial infarction,reflecting part of its scientific connotation of"treating different diseases with the same treatment",and the main focus of treating depression is on the regulation of the central nervous system and endocrine system,which has verified the effectiveness of KXS in the treatment of depression and depression complicating myocardial infarction.
depressiondepression combined with myocardial infarctionKaixin Sannetwork pharmacology
万方数据
维普
