基于网络药理学和实验验证探讨加味丹栀逍遥散治疗抑郁症的作用机制  

Action Mechanism of Modified Danzhi Xiaoyao Powder in Treatment of Depression Based on Network Pharmacology and Experimental Verification

作　　者：李雅静[1] 张长静 刘辉[1] 白明[1] 闫向丽 汪保英[1] 栗俞程[1] 许二平[1] LI Yajing;ZHANG Changjing;LIU Hui;BAI Ming;YAN Xiangli;WANG Baoying;LI Yucheng;XU Erping(Henan University of Chinese Medicine/Zhongjing Key Laboratory of Modern Research on Prescriptions of Henan Province,Zhengzhou Henan China 450046)

机构地区：[1]河南中医药大学/河南省仲景方药现代研究重点实验室,河南郑州450046

出　　处：《中医学报》2024年第1期163-173,共11页Acta Chinese Medicine

基　　金：国家自然科学基金项目(81973739,82274496);河南省优秀青年科学基金项目(202300410249);河南省科技攻关项目(222102310233);河南省博士后科研项目(202001044)。

摘　　要：目的:运用网络药理学方法探究加味丹栀逍遥散治疗抑郁症的作用机制,并通过分子对接和动物实验验证加味丹栀逍遥散治疗抑郁症的潜在靶点。方法:基于中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)、中医药百科全书数据库(The encyclopedia of traditional Chinese medicine,ETCM)等筛选加味丹栀逍遥散的化学成分及作用靶点。使用DisGeNet、人类孟德尔遗传数据库(online mendelian inheritance in man,OMIM)等查询抑郁症相关靶点,并采用STRING扩充二级靶点得到抑郁症的全部靶点。将加味丹栀逍遥散活性成分相关靶点与抑郁症靶点取交集,得到加味丹栀逍遥散治疗抑郁症的相关靶点。借助Cytoscape软件构建蛋白质互作(protein-protein interaction,PPI)网络。使用DAVID对潜在靶点进行基因本体(gene ontology,GO)富集分析和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)信号通路富集分析。通过AutoDock对核心靶点及成分进行分子对接。48只SPF级雄性C57BL/6小鼠随机分为正常组8只和造模组40只,造模组小鼠建立慢性不可预知温和应激(chronic unpredictable mild stress,CUMS)模型,6周后将造模组小鼠分为CUMS组、氟西汀组(20 mg·kg^(-1))及加味丹栀逍遥散低(15.9 kg·L^(-1))、中(31.8 kg·L^(-1))、高(47.7 kg·L^(-1))剂量组,每组8只,以10 mL·kg^(-1)体积灌胃给予相应药物,正常组和模型组灌胃给予等体积的生理盐水,每天1次,持续28天。采用蔗糖偏好实验、悬尾实验和旷场实验评估小鼠的行为学能力;HE染色观察小鼠脑部海马区病理学变化;DCX染色观察海马区新生神经元变化;Western Blot检测PI3K、p-PI3K、AKT、p-AKT及BDNF蛋白表达水平。结果:网络药理学分析显示,加味丹栀逍遥散活性成分164个,对应靶点332个;抑郁症相关靶点1432个;将加味丹栀逍遥散相关靶点和抑郁症相�Objective:To use network pharmacology methods to explore the mechanism of action of modified Danzhi Xiaoyao Powder in the treatment of depression,and to verify the potential targets of modified Danzhi Xiaoyao Powder in the treatment of depression through molecular docking and animal experiments.Method:Based on the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP)and the Encyclopedia of Traditional Chinese Medicine(ETCM),the chemical components and target of action of modified Danzhi Xiaoyao Powder were screened.DisGeNet and the Online Mendelian Inheritance Inman(OMIM)database are used to search for depression related targets,and use STRING to expand secondary targets to obtain all targets of depression.Intersect the targets related to the active ingredients of modified Danzhi Xiaoyao Powder with the targets of depression to obtain the targets related to the treatment of depression with modified Danzhi Xiaoyao Powder.Network Cytoscape software was used to a protein-protein interaction(PPI).Perform gene ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signal pathway enrichment analysis on potential targets by using DAVID.Molecular docking of core targets and components through AutoDock.48 SPF grade male C57BL/6 mice were randomly divided into a normal group of 8 mice and a modeling group of 40 mice.A chronic unpredictable mild stress(CUMS)model was established in the modeling group of mice.After 6 weeks,the modeling group of mice was divided into a CUMS model group,a fluoxetine group(20 mg·kg^(-1)),and a modified Danzhi Xiaoyao powder low(15.9 g·mL^(-1)),medium(31.8 g·mL^(-1)),and high(47.7 g·mL^(-1))dose group,with 8 mice in each group.The corresponding drugs were administered by gavage at a volume of 10 mL·kg^(-1).The normal group and the model group were compared.Administer equal volume of physiological saline by gavage once a day for 28 days.The behavioral ability of mice was evaluated by using sucrose preference experiments,tail suspensi

关 键 词：抑郁症 加味丹栀逍遥散 细胞增殖 神经元新生 网络药理学 分子对接 

分 类 号：R285[医药卫生—中药学]