基于网络药理学及实验验证毓麟珠改善早发性卵巢功能不全大鼠的潜在机制  

Underlying Mechanism of Yulinzhu in Improving POI Rats Based on Network Pharmacology and Experiments

作　　者：阮鑫 魏茂林 董晓英[1] RUAN Xin;WEI Maolin;DONG Xiaoying(School of Chinese Medicine,Capital Medical University,Beijing 100069,China)

机构地区：[1]首都医科大学中医药学院,北京100069

出　　处：《世界中医药》2024年第9期1238-1245,共8页World Chinese Medicine

基　　金：国家自然科学基金青年科学基金项目(81503607);北京市自然科学基金面上项目(7212162);北京中医药薪火传承“3+3”工程项目(2012-SZ-C-41)。

摘　　要：目的:基于网络药理学及动物实验验证探讨毓麟珠改善早发性卵巢功能不全(POI)大鼠的潜在作用机制。方法:采用中药系统药理学数据库与分析平台(TCMSP)数据库筛选毓麟珠中5味核心药物——菟丝子、杜仲、熟地黄、当归、人参的入血活性成分及预测作用靶点,进一步获取药物成分对应靶点及POI靶点,利用微生信平台获取交集靶点,构建蛋白质-蛋白质相互作用网络并筛选出核心靶点,通过DAVID数据库对核心靶点进行基因本体(GO)富集分析及京都基因与基因组百科全书(KEGG)通路富集分析;依据KEGG通路分析结果,选择缺氧诱导因子1(HIF1)信号通路进行动物体内实验验证。结果:筛选出的活性成分主要包括槲皮素、山柰酚、β-谷甾醇、β-胡萝卜素、豆甾醇、芝麻素等。与疾病相关的候选作用靶点共103个,关键靶点涉及蛋白激酶(AKT1)、窖蛋白(CAV1)、雌激素受体1(ESR1)、Ras同源基因家族成员A(RHOA)等,主要参与细胞增殖、介导雌激素发挥生物学作用、细胞信号转导等生物过程。动物实验验证了毓麟珠干预后可改善POI大鼠的血清激素水平,降低HIF1α的蛋白表达水平。结论:毓麟珠通过多靶点、多途径作用于POI,且毓麟珠可能通过HIF1通路改善POI大鼠的卵巢功能。Objective:To explore the underlying mechanism of Yulinzhu in improving premature ovarian insufficiency(POI) in rats based on network pharmacology and animal experiments.Methods:Using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),the active plasma components and predicted targets of five core drugs in Yulinzhu(Cuscutae Semen,Eucommiae Cortex,Rehmanniae Radix Praeparata,Angelicae Sinensis Radix,and Ginseng Radix et Rhizoma) were screened.The corresponding targets of these active components and POI targets were further obtained.Intersection targets were identified using bioinformatics platforms,and a protein-protein interaction(PPI) network was constructed to screen core targets.Gene Ontology(GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed on the core targets using the DAVID database.According to the KEGG pathway analysis results,the hypoxia-inducible factor 1(HIF1) signaling pathway was selected for in vivo validation in animal experiments.Results:The selected core components mainly included quercetin,kaempferol,β-sitosterol,β-carotene,stigmasterol,sesamin,etc.A total of 103 candidate targets related to the disease were identified,with key targets including protein kinase B(AKT1),caveolin-1(CAV1),estrogen receptor 1(ESR1),and Ras homolog family member A(RHOA).These targets were primarily involved in biological processes such as cell proliferation,mediating the biological effects of estrogen,and cell signal transduction.Animal experiments confirmed that Yulinzhu intervention could improve serum hormone levels in POI rats and reduce the protein expression level of HIF1α.Conclusion:Yulinzhu exerts multi-target and multi-pathway effects on POI,and it may improve ovarian function in POI rats through the HIF1 pathway.

关 键 词：毓麟珠 网络药理学 早发性卵巢功能不全 靶点 通路 作用机制 动物实验 缺氧诱导因子1 

分 类 号：R285[医药卫生—中药学] R271.9[医药卫生—中医学]