基于网络药理学和实验验证揭示益血生胶囊治疗缺铁性贫血的作用机制  

Revealing the mechanism of Yixuesheng capsule in treating iron deficiency anemia based on network pharmacology and experimental validation

作　　者：张淑宁 郭叶 张宏[2] 李欢 许爱珍[2] 赵俊立[2] 安明[1] 石贵荣[2] ZHANG Shuning;GUO Ye;ZHANG Hong;LI Huan;XU Aizhen;ZHAO Junli;AN Ming;SHI Guirong(College of Pharmacy,Baotou Medical Collage 014040,China;Pharmacy Deparment,Baotou Central Hospital,Baotou 014040,China)

机构地区：[1]包头医学院药学院,内蒙古包头014040 [2]包头市中心医院药剂科,内蒙古包头014040

出　　处：《沈阳药科大学学报》2025年第2期142-153,共12页Journal of Shenyang Pharmaceutical University

基　　金：内蒙古自治区蒙医药标准化项目(2023MB031);内蒙古自治区自然科学基金面上项目(2023MS08046);中央引导地方科技项目(2022ZY0167);内蒙古自治区高校科研重点项目(NJZZ23105)。

摘　　要：目的基于网络药理学、分子对接及动物实验对中药复方益血生胶囊治疗缺铁性贫血(iron deficiency anemia,IDA)的作用机制进行探讨。方法通过检索相关文献并应用在线数据库获取益血生胶囊及IDA的潜在靶点,构建“活性成分-交集靶点”网络图及蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络,并利用Cytoscape 3.9.1软件筛选出核心基因;采用Metascape数据平台进行GO和KEGG通路富集分析;通过分子对接技术对获得的关键活性成分和核心靶点进行验证分析;建立IDA小鼠模型,进行血常规指标及血浆中铁浓度检测,酶联免疫吸附测定(ELISA)法对网络药理学预测出的核心靶点进行验证,结合结肠病理组织切片及氧化应激指标考察明确益血生胶囊对IDA小鼠的治疗效果。结果共筛选出益血生胶囊治疗IDA的5种关键活性成分,10个核心靶点;GO功能富集分析结果主要涉及细胞激活和炎症反应等生物学过程,KEGG通路富集得到20条主要通路,包括癌症通路和JAK-STAT信号通路等;分子对接显示关键活性成分与核心靶点具有良好的结合能力;动物实验显示,益血生胶囊可以显著改善IDA小鼠血常规指标异常以及结肠组织损伤和炎症,上调血浆中铁浓度、肿瘤坏死因子α(tumor necrosis factor,TNF-α)、血管内皮生长因子(VEGF-A)、信号转导与转录激活因子3(signal transducer and activator of transcription STAT3)及总抗氧化能力(total antioxidant capacity,T-AOC)水平(P<0.01),下调丙二醛(malonaldehyde,MDA)水平(P<0.05)。结论本研究揭示了益血生胶囊通过多成分、多靶点、多通路协同发挥治疗IDA的作用机制,初步验证了益血生胶囊可能通过调控炎症及氧化应激水平对IDA发挥治疗作用,为益血生胶囊抗IDA作用机制的深入研究提供理论依据。Objective Based on network pharmacology,molecular docking and animal experiments,to explore the mechanism of Yixuesheng capsule in treating iron deficiency anemia(IDA).Methods The potential targets of Yixuesheng Capsules and IDA were obtained by searching related literature and applying online database,and the"active ingredient-intersection target"network diagram and protein-protein interaction(PPI)network were constructed,and the core genes were screened out by Cytoscape 3.9.1 software.Using the metascape data platform for GO and KEGG pathway enrichment analysis;Verify and analyze the key active ingredients and core targets obtained through molecular docking technology;Establish an IDA mouse model,detect blood routine indicators and plasma iron concentration,Enzyme-linked immunosorbent assay(ELISA)was used to verify the core targets predicted by network pharmacology,and investigate the therapeutic effect of Yixuesheng Capsule on IDA mice by combining colonic pathological tissue sections and oxidative stress indicators.Results A total of 5 key active components and 10 core targets of Yixuesheng capsule in the treatment of IDA were screened out.GO function enrichment analysis results mainly involve biological processes such as cell activation and inflammatory reaction.KEGG pathway was enriched to obtain 20 main pathways,including cancer pathway and JAK-STAT signal pathway.Molecular docking shows that key active components have good binding ability with core targets;Animal experiments show that Yixuesheng capsule can significantly improve the abnormal blood routine indexes,colon tissue injury and inflammation in IDA mice,up-regulate the plasma iron concentration,tumor necrosis factor α(TNF-α),vascular endothelial growth factor(VEGF-A),signal transduction and transcription activator 3(STAT3),total antioxidant capacity(T-AOC)level(P<0.01),and down-regulate malondialdehyde(MDA)level(P<0.05).Conclusion This study reveals the mechanism of Yixuesheng capsule in treating IDA through multi-components,multi-targets and mu

关 键 词：益血生胶囊 缺铁性贫血 网络药理学 分子对接 炎症 氧化应激 

分 类 号：R28[医药卫生—中药学] R[医药卫生—中医学]