基于网络药理学和分子对接技术及动物实验探究巴亚格七味散对酒精性肝病的作用机制

Exploring the Mechanism of Bayage Qiwei Powder in Treatment of Alcoholic Liver Disease Based on Network Pharmacology,Molecular Docking and Animal Experiment

目的采用网络药理学和分子对接方法探究巴亚格七味散治疗酒精性肝病可能的作用机制,并通过实验进行初步验证。方法利用中药系统药理学数据库分析平台(TCMSP)、Swiss ADME、Swiss Target Prediction和文献获得巴亚格七味散有效成分及其作用靶点;通过GeneCards、DisGeNet和OMIM数据库获取酒精性肝病的疾病靶点;以STRING数据库构建靶点相互作用网络;通过DAVID 6.8数据库对关键靶点进行基因本体(GO)富集分析、京都基因与基因组百科全书(KEGG)通路富集分析。采用Cytoscape 3.7.1软件构建巴亚格七味散治疗酒精性肝病的“药物-有效成分-潜在靶点”网络和“成分-靶点-通路”网络,并筛选关键靶点进行分子对接。基于网络药理学和分子对接结果,通过动物实验初步验证预测结果。结果去重后共获得81个化学成分及906个潜在作用靶点。GO富集分析共得到GO条目510条,其中生物过程365条,细胞组成47条,分子功能98条。KEGG富集共得到106条信号通路,主要涉及神经活性配体-受体相互作用、趋化因子信号通路、Fc RI信号通路等通路。分子对接结果显示,MAP2K1、MAPK1和PIK3CA等靶点可能为巴亚格七味散治疗酒精性肝病的关键靶点。体内动物实验结果表明,巴亚格七味散可以有效减少酒精性肝病小鼠干细胞坏死和脂滴堆积的程度,从而缓解肝组织的病变,同时可以降低MAPK1和PIK3R1的表达,与网络模拟结果基本一致。结论初步揭示巴亚格七味散可能是通过影响MAPK1和PIK3R1的表达,减轻炎性细胞浸润和肝细胞坏死程度,从而起到治疗酒精性肝病的作用,可为深入阐明巴亚格七味散治疗酒精性肝病分子机制提供理论依据。

Objective Network pharmacology and molecular docking were adopted to explore the possible mechanism of Bayage Qiwei powder for alcoholic liver disease.To preliminarily verify the predicted results by experiments in vivo.Methods The active components of Bayage Qiwei powder and their potential targets were obtained from the database analysis platform of traditional Chinese medicine system pharmacology,Swiss ADME,Swiss Target Prediction and literature.GeneCards,DisGeNet and OMIM database were used to obtain disease targets of alcoholic liver disease.STRING database was used to build the interaction network of targets.Gene body(GO)enrichment analysis and Kyoto Gene and Genome Encyclopedia(KEGG)pathway enrichment analysis of key targets were conducted through DAVID 6.8 database.Using Cytoscape 3.7.1 software,the“drug-active components-target”and“constituent-target-pathway”networks of Bayage Qiwei powder were constructed,and the key targets were selected for molecular docking.Based on the results of network pharmacology and molecular docking,the prediction results were verified by animal experiments.Results A total of 81 chemical constituents and 906 potential targets were obtained after deweighting.GO enrichment analysis yielded 510 GO entries(P<0.05),365 of which were biological processes,47 were cellular components,and 98 were molecular functions.KEGG enrichment resulted in 106 signaling pathways(P<0.05),mainly involved in neuroactive ligand-receptor interaction,Fc epsilon RI signaling pathway and chemokine signaling pathway.Docking results illustrated that MAP2K1,MAPK1 and PIK3CA may be the key target of Bayage Qiwei powder in the treatment of alcoholic liver disease.The results of animal experiments showed that Bayage Qiwei powder could effectively reduce the degree of stem cell necrosis and lipid droplet accumulation in mice with alcoholic liver disease,and reduce the expression of MAPK1 and PIK3R1,which was consistent with the simulation results.Conclusion This study preliminarily predicted that Bayage Qiwei powder may play a role in the treatment of alcoholic liver disease by affecting the expression of MAPK1 and PIK3R1,alleviating inflammatory cell infiltration and hepatocyte necrosis.It provided a theoretical basis for further elucidating the molecular mechanism of Bayage Qiwei powder in the treatment of alcoholic liver disease.