现代中西医结合杂志2025，Vol.34Issue(19)：2656-2663,2680,9.DOI:10.3969/j.issn.1008-8849.2025.19.005
基于转录组学联合网络药理学探讨柴胡-白芍治疗肝郁脾虚型抑郁症的机制
Mechanism of Bupleuri Radix-Paeoniae Radix Alba in the treatment of depression with syndrome of liver-depression and spleen-deficiency based on transcriptomics with network pharmacology
摘要
Abstract
Objective It is to screen the differentially expressed genes(DEGs)in the liver tissues of rats with depres-sion with syndrome of liver-depression and spleen-deficiency compared with normal rats based on RNA-seq technology,and to screen the targets and pathways of the therapeutic effects of Bupleuri Radix-Paeoniae Radix Alba by network pharmacolo-gy,so as to provide references for the in-depth study and clinical application of the drug pair.Methods Ten SD male rats were randomly divided into depression group and normal group,and the rats of the depression group were prepared by chro-nic unpredictable mild stress(CUMS)to establish models of depression with syndrome of liver-depression and spleen-defi-ciency.The general signs of the rats were observed,their body weights were recorded and behavioral tests were carried out every 7 days,including absenteeism experiments,forced-swimming experiments and sugar-water preference experiment.After 28 days of modeling,the liver tissues of rats in each group were taken for transcriptome sequencing,the differentially expressed genes(DEGs)in the liver tissues of rats in the two group were obtained,then they were analyzed by GO function enrichment analysis and KEGG pathway enrichment analysis,to screen the intersection of the target of action of Bupleuri Radix-Paeoniae Radix Alba with the differentially expressed genes by network pharmacology,and PPI protein network inter-actions were analyzed,and a"drug-component-target-pathway"network diagram was constructed to predict the gene targets and pathways related to the treatment of depression with syndrome of liver-depression and spleen-deficiency with Bupleuri Radix-Paeoniae Radix Alba.Results On the 28th day of experiment,the rats in the depression group exhibited dry,knot-ted hair,lethargy,reduced activity,sluggish movements,and dulled responses,their feces were loose and bad smelling,their body weight,time of grid crossings in the horizontal movement test,and sugar water preference index were all signifi-cantly lower than those of rats in the normal group(all P<0.05),while their immobility time in the swimming test was significantly longer than that in the normal group(P<0.05).Transcriptome sequencing analysis showed that a total of 383 genes were significantly up-regulated and 493 genes were significantly down-regulated in the rats of model group compared with the normal group.The GO function enrichment analysis and KEGG pathway enrichment analysis showed that the differ-ential genes were mainly involved in the process of regulation of glucose-lipid metabolism and insulin secretion,as well as the circadian rhythm process,specifically,there were negative regulation process of insulin secretion,AMPK signaling pathway,PPARγ signaling pathway and so on.Combined with the results of network pharmacological analysis,the treat-ment of depression with composition of Bupleuri Radix-Paeoniae Radix Alba may be related to regulate the expression of genes such as Pparg and Cpt1a,and thus to regulating AMPK signaling pathway,PPARγ signaling pathway,and so on.Conclusion There were numerous differentially expressed genes in liver,along with abnormal liver metabolism in the rats with depression with syndrome of liver-depression and spleen-deficiency compared with normal rats.Acting on genes such as Pparg to regulate signaling pathways including AMPK and PPARγ may be one of the key mechanisms of drug pair Bu-pleuri Radix-Paeoniae Radix Alba in the treatment of depression with syndrome of liver-depression and spleen-deficiency.关键词
抑郁症/肝郁脾虚/柴胡-白芍/转录组/AMPK信号通路/PPARγ信号通路Key words
depression/syndrome of liver-depression and spleen-deficiency/Bupleuri Radix-Paeoniae Radix Alba/transcriptome/PPARγ signaling pathway分类
医药卫生引用本文复制引用
于莎莎,耿少辉,付婧媛,姜懿津,叶子,肖恩凡,黄光瑞..基于转录组学联合网络药理学探讨柴胡-白芍治疗肝郁脾虚型抑郁症的机制[J].现代中西医结合杂志,2025,34(19):2656-2663,2680,9.基金项目
北京市大学生创新创业训练计划(X202410026077) （X202410026077）
北京高校大学生创新创业训练校际合作计划(202498132) （202498132）
