基于网络药理学及实验验证探讨枳实栀子豉汤抗抑郁症的作用机制  

Exploring the action mechanism of anti-depression of Zhishi Zhizichi Soup based on network pharmacology and experimental validation

作　　者：赵权 张卫东[1] 张晶[1] 蒋婷 颜晓静[2] 王地均 周政 华丰 ZHAO Quan;ZHANG Weidong;ZHANG Jing;JIANG Ting;YAN Xiaojing;WANG Dijun;ZHOU Zheng;HUA Feng(Department of Pharmacy,Changzhou Hospital of Traditional Chinese Medicine,Nanjing University of Chinese Medicine,Jiangsu Province,Changzhou213003,China;Menghe Medical Institute,Changzhou Affiliated Hospital,Nanjing University of Chinese Medicine,Jiangsu Province,Changzhou213003,China)

机构地区：[1]南京中医药大学附属常州市中医医院药学部,江苏常州213003 [2]南京中医药大学常州附属医院孟河医学研究所,江苏常州213003

出　　处：《中国医药导报》2024年第21期18-26,共9页China Medical Herald

基　　金：国家自然科学基金资助项目(82074016、81603296);江苏省常州市科技计划(应用基础研究指导性)项目(CJ20239042、CJ20229029);江苏省常州市中医医院科研基金资助项目(QN202309)。

摘　　要：目的通过网络药理学预测枳实栀子豉汤抗抑郁的作用靶点及信号通路,并进行实验验证。方法采用中药系统网络药理学数据库与分析平台筛选枳实栀子豉汤的活性成分并预测其作用靶点,通过OMIM、GeneCards检索抑郁症的潜在疾病靶点,选取成分与疾病的交集靶点作为蛋白靶点库,采用STRING获取交集靶点蛋白相互作用的网络,通过Cytoscape软件对数据进行可视化分析,构建活性成分-预测靶点-信号通路网络。通过蛋白质-蛋白质相互作用分析枳实栀子豉汤的关键靶点并进行动物实验。同时,采用DAVID数据库进行基因本体(GO)和京都基因和基因组数据库(KEGG)富集分析,综合评价枳实栀子豉汤抗抑郁的作用机制。30只SD大鼠适应性喂养1周后,随机分为正常组6只,造模组24只。除正常组外,实验大鼠均接受慢性温和不可预知应激造模,确认造模成功后,将造模组按随机数字表法分为四组,高剂量组(13.32 g/kg枳实栀子豉汤)、中剂量组(6.66 g/kg枳实栀子豉汤)、低剂量组(3.33 g/kg枳实栀子豉汤)、模型组,每组6只,对其进行动物行为学和蛋白质印迹法实验。结果筛选出38个枳实栀子豉汤的有效活性成分,预测出枳实栀子豉汤治疗抑郁症的潜在靶点52个,关键靶点筛选出ERK、CREB、BDNF作为验证通路。GO和KEGG分析结果显示,枳实栀子豉汤治疗抑郁症涉及FoxO信号通路、MAPK信号通路、催乳素信号通路、雌激素信号通路、ErbB信号通路、GnRH信号通路、鞘脂信号通路等多个信号通路。实验动物行为学实验结果显示,与正常组比较,模型组糖水偏好率下降,游泳不动时间上升,旷场实验的水平得分和垂直得分均降低(P<0.01)。与模型组比较,低、中剂量组糖水偏好率上升(P<0.05);与模型组比较,中、高剂量组游泳不动时间减少(P<0.05);与模型组比较,低、中、高剂量组垂直得分升高(P<0.05);与模型组比较,低、中剂量Objective To predict the action target of anti-depression and signalling pathway of Zhishi Zhizichi Soup by network pharmacology and to experimentally validate it.Methods The active ingredients of Zhishi Zhizichi Soup were screened and their action targets were predicted using the Systems Pharmacology database and analysis platform,the potential disease targets of depression were retrieved through OMIM and GeneCards,and the intersecting targets of the ingr-edients and the diseases were selected as the protein target libraries,and STRING was used to obtain the network of the intersecting target-protein interactions,and the data were analysed through the Cytoscape software for the Visualisation analysis was performed to construct the active ingredient-predicted target- signalling pathway network. The key targets of Zhishi Zhizichi Soup were analysed by proteinprotein interaction and animal experiments were performed. Meanwhile, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using the DAVID database to comprehensively evaluate the antidepressant mechanism of action of Zhishi Zhizichi Soup. After 30 SD rats were acclimatised and fed for one week, they were randomly divided into six in the normal group and 24 in the modelling group. Except for the normal group, the experimental rats were subjected to chronic unpredictable mild stress, and after confirming the success of modelling, the modelling group was divided into four groups according to the random number table method, the high-dose group (13.32 g/kg Zhishi Zhizichi Soup), the medium-dose group (6.66 g/kg Zhishi Zhizichi Soup), the low-dose group (3.33 g/kg Zhishi Zhizichi Soup), and model group, with six animals in each group, on which animal behavioural and Western blotexperiments were performed. Results Thirty-eight effective active ingredients of Zhishi Zhizichi Soup were screened, and 52 potential targets of Zhishi Zhizichi Soup for the treatment of depression were predicted, and the key targets were s

关 键 词：枳实栀子豉汤 抑郁症 网络药理学 作用机制 

分 类 号：R246.6[医药卫生—针灸推拿学]