基于网络药理学及蛋白质组学探讨优韧集胶囊改善骨质疏松的作用机制  

Study on mechanism of Yourenji Capsules in improving osteoporosis based on network pharmacology and proteomics

作　　者：高云航 李晗 李建良[1] 宋玲 陈腾飞 侯红平[1] 彭博[1] 李鹏 张广平[1] GAO Yun-hang;LI Han;LI Jian-liang;SONG Ling;CHEN Teng-fei;HOU Hong-ping;PENG Bo;LI Peng;ZHANG Guang-ping(Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China;Hebei Yuzhilin Biotechnology Co.,Ltd.,Shijiazhuang 050000,China)

机构地区：[1]中国中医科学院中药研究所,北京100700 [2]河北御芝林生物科技有限公司,河北石家庄050000

出　　处：《中国中药杂志》2025年第2期515-526,共12页China Journal of Chinese Materia Medica

基　　金：国家重点研发计划项目(2018YFC1602103)。

摘　　要：应用网络药理学与蛋白质组学技术,探讨优韧集胶囊(Yourenji Capsules,YRJ)改善骨质疏松可能的药效作用机制。将SD大鼠随机分为空白对照组和700 mg·kg^(-1)YRJ组,灌胃给予相应药物,利用UPLC-Q-TOF-MS/MS比较空白血清、含药血清和YRJ样品,分析主要入血成分。基于YRJ入血成分进行网络药理学分析,获取入血成分相关靶点及骨质疏松疾病涉及靶基因,绘制韦恩图获取药物作用靶点与疾病靶点的交集。采用STRING数据库进行潜在作用靶点的蛋白-蛋白互作(PPI)网络分析,构建PPI网络。利用Enrichr进行GO功能富集和KEGG通路富集,探究YRJ的潜在作用机制。采用双侧卵巢去势法(OVX)构建大鼠骨质疏松模型,分为假手术组、模型组和700 mg·kg^(-1)YRJ组,灌胃给予相应药物。取大鼠股骨进行非标记蛋白质组学技术(Label-free)检测各组间差异蛋白的表达,并进行差异蛋白的GO功能和KEGG通路富集分析。结合网络药理学和蛋白质组学结果预测YRJ改善骨质疏松的作用机制。入血成分结果显示,YRJ血清入血成分23个,入血成分网络药理学结果显示,涉及肿瘤坏死因子(TNF)、肿瘤抑制蛋白53(TP53)、蛋白激酶(AKT1)、基质金属蛋白酶9(MMP9)等核心靶点,主要参与破骨细胞分化、雌激素信号通路、核因子κB(NF-κB)信号通路等;蛋白质组学涉及过氧化物酶体增殖物激活受体(PPAR)信号通路、丝裂原激活蛋白激酶(MAPK)信号通路、β-丙氨酸代谢等重要通路。网络药理学和蛋白质组学共同揭示了YRJ改善骨质疏松的作用机制可能与调控炎症、成骨细胞和破骨细胞代谢通路密切相关,主要通路包括NF-κB信号通路、MAPK信号通路、PPAR信号通路等。This study aimed to explore the pharmacological mechanism of Yourenji Capsules(YRJ)in improving osteoporosis by combining network pharmacology and proteomics technologies.The SD rats were randomly divided into a blank control group and a 700 mg·kg^(-1)YRJ group.The rats were subjected to gavage administration with the corresponding drugs,and the blank serum,drugcontaining serum,and YRJ samples were compared using ultra performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS)to analyze the main components absorbed into blood.Network pharmacology analysis was conducted based on the YRJ components absorbed into blood to obtain related targets of the components and target genes involved in osteoporosis,and Venn diagrams were used to identify the intersection of drug action targets and disease targets.The STRING database was used for protein-protein interaction(PPI)network analysis of potential target proteins to construct a PPI network.Gene Ontology(GO)functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment were performed using Enrichr to investigate the potential mechanism of action of YRJ.Ovariectomy(OVX)was performed to establish a rat model of osteoporosis,and the rats were divided into a sham group,a model group,and a 700 mg·kg^(-1)YRJ group.The rats were given the corresponding drugs by gavage.The femurs of the rats were subjected to label-free proteomics analysis to detect differentially expressed proteins,and GO functional enrichment and KEGG pathway enrichment analyses were performed on the differentially expressed proteins.With the help of network pharmacology and proteomics results,the mechanism by which YRJ improves osteoporosis was predicted.The analysis of the YRJ components absorbed into blood revealed 23 bioactive components of YRJ,and network pharmacology results indicated that key targets involved include tumor necrosis factor(TNF),tumor protein p53(TP53),protein kinase(AKT1),and matrix metalloproteinase 9(MMP9).These

关 键 词：优韧集胶囊 骨质疏松 双侧卵巢去势模型 网络药理学 蛋白质组学 

分 类 号：R285.5[医药卫生—中药学]