| 引用本文:李新宝1，庞欣欣2，彭紫凝1，商海涛1，朱清1，郑威1，韩佳瑞1，2.基于生物信息学及动物实验对芪黄固肾通络方治疗糖尿病肾病的研究[J].世界中医药,2024,(05):. |
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| 基于生物信息学及动物实验对芪黄固肾通络方治疗糖尿病肾病的研究 |
| Study on Qihuang Gushen Tongluo Prescription in Treating Diabetic Nephropathy Based on Bioinformatics and Animal Experiment |
| 投稿时间：2022-10-07 |
| DOI：10.3969/j.issn.1673-7202.2024.05.002 |
| 中文关键词: 芪黄固肾通络方；糖尿病肾病；网络药理学；动物实验；晚期糖基化终末产物-晚期糖基化终末产物受体；连环蛋白β JUN 核受体辅激活蛋白1 |
| English Keywords:Qiguangushen Tongluo Prescription Diabetic nephropathy Network pharmacology Animal experiment AGE-RAGE CTNNB1 JUN NCOA1 |
| 基金项目:河南省重点研发与推广专项（科技攻关）项目（202102310171，202102310505）；国家中医临床研究基地科研项目（2019JDZX068）；河南省中医药拔尖人才培养项目专项课题（2019ZYBJ17）；全国中医药创新骨干人才培养项目（无）；河南省中医药科学研究专项重点课题（20-21ZY1003）；河南省中医药拔尖人才培养项目（2019ZYBJ17） |
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| 中文摘要: |
| 目的：探讨芪黄固肾通络方治疗糖尿病肾病(DKD)的作用机制。方法：通过人类基因数据库(GeneCards)、治疗靶点数据库(TTD)、人类疾病相关基因和突变基因数据库（DisGeNET）、综合性药物数据库（DrugBank）等数据库查找芪黄固肾通络方的活性成分、作用靶点、DKD相关的靶点。将药物目标点与病变靶点进行映射，将所获得的交集目标点构造蛋白质-蛋白质相互作用（PPI）网络与活性组分-联合目标网络，并进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析。通过动物实验对网络药理学结果中芪黄固肾通络方治疗糖尿病肾病核心靶点中富集节点较多的前3靶点进行验证。选取C57BL/6J小鼠为研究对象，链脲佐菌素（STZ）连续2次腹腔注射制备动物模型，8周后测小鼠24 h尿蛋白定量，分为正常组、模型组、模型+芪黄固肾通络方组，干预8周后，测胰岛素、C肽、尿素氮、24 h尿蛋白定量，qPCR及蛋白质印迹法（Western Blotting）检测小鼠肾脏CTNNB1、JUN、NCOA1表达。结果：GO与KEGG富集分析显示芪黄固肾通络方治疗DKD的有效靶点主要涉及晚期糖基化终末产物-晚期糖基化终末产物受体（AGE-RAGE）信号通路、血脂和动脉粥样硬化、流体剪切应力与动脉粥样硬化、神经活性配体-受体交互作用等；动物实验表明，芪黄固肾通络方能够降低DKD小鼠肾组织中连环蛋白β1（CTNNB1）、JUN、核受体辅激活蛋白1（NCOA1）的信使核糖核酸（mRNA）及蛋白表达，改善肾脏损伤。结论：通过网络药理学和实验验证，发现芪黄固肾通络方可能通过降低CTNNB1、JUN、NCOA1蛋白的表达水平干预AGE-RAGE等通路治疗DKD。 |
| English Summary: |
| In this study，the mechanism of Qiguangushen Tongluo Prescription in the treatment of diabetic nephropathy(DKD) was investigated.Methods:The active components and targets of Qighuanggu Shen Tongluo Prescription and the DKD-related targets were searched from GeneCards，TTD，DisGeNET，DrugBank，and other databases.The drug target points were mapped to the lesion target points，and the obtained intersection target points were constructed into a protein-protein interaction(PPI) network and active component-joint target network.Gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) enrichment analyses were performed.Animal experiments were conducted to verify the first three targets with more enrichment nodes in the core targets of DKD treated by Qihuanggushen Tongluo Prescription in the network pharmacology results.C57BL/6J mice were selected as the study objects，and streptozotocin(STZ) was injected intraperitoneally twice to prepare the animal model.After eight weeks，24 h urinary protein of the mice was measured，and the mice were divided into the normal group，model group，and model+Qihuanggushen Tongluo Prescription group.After eight weeks of intervention，insulin，C-peptide，urea nitrogen，and 24 h urinary protein were measured.The expressions of CTNNB1，JUN，and NCOA1 in mouse kidneys were detected by quantitative polymerase chain reaction(qPCR) and Western blot.Results:GO and KEGG enrichment analyses showed that the effective targets of Qihuanggushen Tongluo Prescription in the treatment of DKD mainly involved the AGE-RAGE signaling pathway，lipid and atherosclerosis，fluid shear stress and atherosis，neuroactive ligand-receptor interaction，etc.Animal experiments showed that Qihuanggushen Tongluo Prescription could reduce the mRNA and protein expressions of CTNNB1，JUN，and NCOA1 in the kidney tissue of DKD mice and improve kidney injury.Conclusion:Through network pharmacology and experimental verification，it is found that Qihuanggushen Tongluo Prescription may intervene in AGE-RAGE and other pathways to treat DKD by reducing the expression levels of CTNNB1，JUN，and NCOA1 proteins. |
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