摘要
目的 基于入血成分分析联合网络药理学探讨引火汤(YHD)对围绝经期抑郁症(PMD)大鼠抑郁样行为的改善作用及机制。方法 用双侧卵巢摘除(OVX)联合慢性不可预知性温和刺激(CUMS)方法复制PMD模型。实验分为假手术组、模型组和YHD组。假手术组和模型组均灌胃给予等量0.9%NaCl,qd;YHD组灌胃给予4.05 g·kg^(-1 )YHD,qd。3组大鼠均连续给药3周。用强迫游泳实验观察YHD对PMD大鼠抑郁行为的影响,用苏木精-伊红染色和高尔基染色法观察YHD对PMD大鼠的神经保护作用。用超高效液相色谱-四极杆-飞行时间串联质谱技术分析YHD入血成分,用基因名片数据库和网络可视化软件Cytoscape3.7.1对核心靶基因进行生物功能分析和京都基因与基因组百科全书通路富集分析,并用分子对接技术验证预测结果。结果 假手术组、模型组和YHD组的不动时间分别为(94.34±15.68)、(158.00±16.44)和(100.34±5.00)s。与假手术组比较,模型组的强迫游泳不动时间明显增加(P<0.01),海马神经元排列松散无序,有核固缩现象,树突棘密度减少;与模型组比较,YHD组的强迫游泳不动时间明显降低(P<0.01),海马神经元排列较为紧密,数量较多,形态正常,树突棘密度有明显增加。YHD含药血清成分分析共鉴定出12种原型入血成分,分子对接结果显示麦冬二氢高异黄酮E、甲基麦冬高异黄酮A、去氢土莫酸与主要靶点白蛋白、蛋白激酶B(Akt)1、胱天蛋白酶3能够最佳结合。结论 YHD可改善OVX+CUMS大鼠抑郁样行为,恢复海马神经元形态,增加树突棘密度,其机制可能是通过调控磷脂酰肌醇-3激酶-Akt信号通路和促分裂原活化蛋白激酶信号通路实现的。
Objective To explore the improving effect and mechanism of Yinhuo decoction (YHD) on depressive behaviors in perimenopausal depression (PMD) rats based on blood components analysis and network pharmacology.Methods The PMD model was replicated using bilateral ovariectomy (OVX) combined with chronic unpredictable mild stimulation (CUMS).The experiment was divided into sham-operation,model and YHD groups.The sham-operation and model groups were given an equal amount of 0.9%NaCl by gavage,qd;the YHD group was given 4.05 g·kg^(-1)YHD by gavage,qd.Three groups were continuously administered for 3 weeks.The effect of YHD on depressive behavior in PMD rats using forced swimming experiments was observed,and the neuroprotective effect of YHD on PMD rats using hematoxylin eosin staining and Golgi staining methods was observed.Ultra high performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry was used to analyze the blood components of YHD,and the core target genes were enriched by biological functional analysis and Kyoto encyclopedia of genes and genomes pathways using GeneCards and network visualization software Cytoscape3.7.1,and the prediction results were verified by molecular docking technology.Results The immobility time of the sham-operation,model and YHD groups was (94.34±15.68),(158.00±16.44) and (100.34±5.00) seconds,respectively.Compared with the sham-operation group,the forced swimming immobility time of the model group rats increased (P0.01),the hippocampal neurons arranged loosely and disorderly,with pyknosis,and the density of dendritic spine decreased.Compared with the model group,the forced swimming immobility time of YHD group rats was reduced (P0.01),the hippocampal neurons were arranged more closely,the number was more,the morphology was normal,and the density of dendritic spine was significantly increased.A total of 12 prototype blood components were identified through the analysis of YHD drug containing serum components.Molecular docking results showed that the dihydro
作者
吴东雪
张悦
张莉莉
李月
徐红丹
刘国良
薛慧
赵继会
胡晶
张宁
WU Dong-xue;ZHANG Yue;ZHANG Li-li;LI Yue;XU Hong-dan;LIU Guo-liang;XUE Hui;ZHAO Ji-hui;HU Jing;ZHANG Ning(College of Pharmacy,Heilongjiang University of Chinese Medicine,Harbin 150040,Heilongjiang Province,China;Department of Pharmacy,Wuxi Higher Health Vocational Technology School,Wuxi 214028,Jiangsu Province,China;College of Pharmacy,Hunan University of Medicine,Huaihua 418000,Hunan Province,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2023年第20期2946-2950,共5页
The Chinese Journal of Clinical Pharmacology
基金
国家自然科学基金青年基金资助项目(82003975)
黑龙江省自然科学基金联合引导课题资助项目(LH2020H101)
江苏高校“青蓝”工程优秀青年骨干教师培养基金资助项目
无锡市卫生健康委科研项目面上基金资助项目(M202170)
黑龙江中医药大学基金面上基金资助项目(201819)
黑龙江中医药大学工程中心课题资助项目(2017SEC02)。
关键词
引火汤
围绝经期抑期抑郁症
入血成分
网络药理学
分子对接
Yinhuo decoction
perimenopausal depression
blood ingredient
network pharmacology
molecular docking
