基于生物信息学整合分析醒脾舒肝汤调节自噬治疗中医郁病的分子机制

目的:利用生物信息学方法,对醒脾舒肝汤进行多成分、多靶点、多通路、多miRNA研究,分析其在增强自噬发挥抗抑郁的作用及分子机制,为进一步开发醒脾舒肝汤提供理论依据。方法:利用TCMSP数据库收集醒脾舒肝汤活性化合物并进行初步筛选。采用Swiss Target Prediction数据库预测活性化合物靶点,通过GeneCards数据库预测中医郁病对应的西医病名焦虑症、抑郁症、躯体形式障碍的作用靶点,交集靶点得出"中药—疾病—表型"共同靶点。采用String数据库进行PPI网络构建,利用Cytoscape软件进行MCODE、MCC及拓扑分析整合得出共同靶点关键基因。采用WebGestalt数据库进行GO、KEGG富集分析及聚类亚网络分析。采用TargetScan数据库对关键基因mRNA进行反向预测其miRNA,构建miRNA-mRNA互作关系网络调控模式。结果:醒脾舒肝汤中有效高活性化合物:麻黄10个,红花12个,川芎6个,细辛6个,艾叶7个,柴胡9个,吴茱萸21个,白术4个,白芍3个,香附10个;"中药—疾病—表型"共同靶点312个,整合算法分析后获得39个关键基因;富集分析结果得出醒脾舒肝汤在细胞膜区改变膜蛋白结构,影响蛋白与蛋白、RNA、DNA结合,影响细胞内信号传导的生物进程抗抑郁,其机制可能与网络化调控多通路机制介导自噬增强有关;miRNA-mRNA相互作用模式可能调控自噬发挥抗抑郁作用。结论:醒脾舒肝汤多成分、多靶点、多通路、多miRNA参与增强自噬机制发挥抗抑郁作用,为中医郁病治疗,西医抑郁症、焦虑症、躯体形式障碍治疗提供理论靶点及临床预测标志物,推进中西医结合诊断治疗郁病的发展。

Bioinformatics Data Integration-based Analysis of the Molecular Mechanism of Xingpi Shugan Decoction in Regulating Autophagy in Depression Treatment

Objective:By using bioinformatics methods on research Xingpi Shugan Decoction with multi-component,multi-target,multi-pathway,and multi-miRNA,to analyze its antidepressant effect and molecular mechanism in autophagy enhancement and provide a theoretical basis for further development of Xingpishugan Decoction.Methods:Use the TCMSP database to collect active compounds of Xingpi Shugan Decoction and conduct preliminary screening.Use the Swiss Target Prediction database to predict active compound targets.Use the GeneCards database to predict the target points of depression in TCM(Chinese medicine)with its corresponded western medicine name:anxiety disorder;depressive disorder,and somatoform disorder.Obtain the common targets of"Chinese medicine-Disease-Phenotype"by integrated algorithm analysis.Established the common target genes by using the String database for PPI network integration,Cytoscape software for MCODE,MCC,and topological analysis integration.Use the WebGestalt database for GO,KEGG enrichment analysis,and clustering sub-network analysis.Use the TargetScan database to reversely predict the miRNA of key gene mRNA,and construct a miRNA-mRNA interaction relationship network conversion model.Results:Effective and highly active compounds exist in Xingpi Shugan Decoction,details are as follow:10 in Mahuang,12 in Honghua,6 in Chuanxiong,6 in Xixin,7 in Aiye,9 in Chaihu,21 in Wuzhuyu,4 Baishu,3 in Baishao,and 10 in Xiangfu;The"Chinese Medicine-Disease-Phenotype"has 312 common targets,39 common target genes were obtained after the integrated algorithm analysis;The result of enrichment analysis indicates that Xingpi Shugan Decoction mainly changes the membrane protein structure in the cell membrane area,affects the binding between proteins,RNA,and DNA,and affects the biological anti-depression process of intracellular signal transduction,its mechanism may be mediated by a multi-pathway mechanism of network regulation related to autophagy enhancement,And the miRNA-mRNA interaction mode may participate in autophagy regulation and anti-depressant effects.Conclusion:Xingpi Shugan Decoction participates in the autophagy enhancement mechanism with multi-component,multi-target,multi-pathway,multi-miRNA and has anti-depressant effect,it also provides theoretical targets and clinical predictive markers for the treatment of depression in TCM and for depressive disorder,anxiety disorder,and somatoform disorder in Western medicine,which can boost the integration between TCM and Western medicine on diagnosis and treatment of Depression.