基于网络药理学和动物实验探究引火汤治疗围绝经期抑郁症的机制  

Effect of Yinhuo decoction for perimenopausal depression based on network pharmacology and animal experiment

作　　者：张莉莉 王堰 刘爽 赵红梅 赵灿 周玉 赵巧玲 徐红丹 ZHANG Lili;WANG Yan;LIU Shuang;ZHAO Hongmei;ZHAO Can;ZHOU Yu;ZHAO Qiaoling;XU Hongdan(Pharmaco-logy Laboratory of Traditional Chinese Medicine,School of Pharmacy,Heilongjiang University of Chinese Medicine,Harbin 150040,China;Department of Pharmacy,Wuxi Health Higher Vocational and Technical School)

机构地区：[1]黑龙江中医药大学药学院中药药理实验室,哈尔滨150040 [2]无锡卫生高等职业技术学校药学系

出　　处：《山西医科大学学报》2024年第10期1335-1342,共8页Journal of Shanxi Medical University

基　　金：无锡市卫生健康“双百”战略中青年医疗卫生拔尖人才培养计划项目(BJ2023094);江苏高校“青蓝工程”优秀青年骨干教师培养项目;无锡市卫生健康委科研项目(M202333)。

摘　　要：目的 基于网络药理学探讨引火汤(Yinhuo decoction,YHD)治疗围绝经期抑郁症(perimenopausal depression,PMD)的潜在机制。方法 利用中药系统药理学数据库与分析平台(TCMSP)和中医药综合数据库(TCM-ID)筛选YHD的活性成分及作用靶点,通过GeneCards数据库和Drugbank数据库筛选PMD疾病相关靶点,使用蛋白质相互作用数据库(STRING)得到疾病靶点和成分靶点的交集基因,利用Cytoscape软件筛选出核心靶点,并构建活性成分-核心靶点-疾病网络。小鼠分为假手术组(sham组)、模型组(PMD组)、引火汤组(YHD组)和雌二醇组(E_(2)组),每组12只。采用卵巢切除法结合慢性不可预见性温和刺激方法建立PMD模型。sham组摘取同样大小脂肪团代替卵巢;YHD组和E_(2)组造模结束后分别给予引火汤和戊酸雌二醇溶液21 d。通过糖水偏好实验和旷场实验检测各组小鼠行为学变化;免疫荧光染色小胶质细胞标志蛋白Iba-1观察各组小鼠海马区小胶质细胞活化水平;ELISA法检测各组小鼠海马中TNF-α和IL-1β水平。结果 共筛选出YHD活性成分对应靶点620个,疾病靶点994个,成分靶点与疾病靶点的交集靶点253个,核心靶点47个,包括TNF-α、IL-1β、NF-κB等。通过Cytoscape3.7.1软件构建“引火汤活性成分-核心靶点-疾病”网络,并得到引火汤的核心成分为戈米辛R、5-羟甲基糠醛、二氢高异黄酮B、12-羟甲基糠醛、麦冬二氢高异黄酮A等。动物实验结果表明,与sham组比较,E_(2)组和YHD组小鼠糖水偏好率、中央区域活动路程比值、直立次数和中央区域活动路程明显增加(P<0.01);与PMD组相比,E_(2)组和YHD组小鼠活化的小胶质细胞形态趋于正常生理状态,Iba-1表达减少(P<0.01),海马区TNF-α和IL-1β含量降低(P<0.01)。结论 YHD可以通过降低PMD小鼠海马区Iba-1、TNF-α、IL-1β表达水平,抑制小胶质细胞过度活化而发挥抗抑郁作用。Objective To explore the potential mechanism of Yinhuo decoction(YHD)treating perimenopausal depression(PMD)based on network pharmacology.Methods The active ingredients and targets of YHD were retrieved from TCMSP and TCM‐ID.The disease‐related targets were retrieved from GeneCards and DrugBank databases.The intersection targets of the drugs and the disease‐related targets were identified using STRING online tool.Cytoscape software was utilized to screen the core targets and construct the active ingredient‐core target‐disease network.The mice were divided into sham group,model group(PMD group),YHD group and estradiol group(E_(2) group),with 12 mice in each group.PMD model was established by ovariectomy combined with chronic unpredict‐able mild stimulation method.The mice in sham group were performed the removal of the same size of fat mass instead of the ovary,and the mice in YHD group and E_(2) group were treated with YHD and estradiol valerate solution for 21 d after the successful modeling,respectively.Behavioral changes of mice were detected by the sugar‐water preference experiment and the open field experiment.Immu‐nofluorescence staining of microglia marker protein Iba‐1 was used to observe the activation level of microglia in the hippocampus of mice.TNF‐αand IL‐1βlevels in the hippocampus of mice in each group were detected by ELISA.Results A total of 620 targets cor‐responding to YHD active ingredients,994 disease targets,253 ingredient‐disease intersection targets,and 47 core targets(TNF‐α,IL‐1β,and NF‐κB),were screened.Cytoscape 3.7.1 software was used to construct the active ingredients‐core target‐disease network,and the core ingredients of YHD were found to be gomisin R,5‐hydroxymethylfurfural,dihydrohomoisoflavone B,12‐hydroxymethyl‐furfural,and maitake dihydrohomoisoflavone A.Compared with sham group,sugar‐water preference rate,central activity distance ratio,number of uprights and central activity distance were significantly increased in E_(2) group

关 键 词：引火汤 围绝经期抑郁症 网络药理学 神经炎症 小胶质细胞活化 TNF-α IL-1Β NF-κB 

分 类 号：R96[医药卫生—药理学]