摘要
目的通过网络药理分析及相关的动物实验探讨黄芪减少糖尿病肾病蛋白尿(Diabetic nephropathy proteinuria,DNP)的作用机制。方法利用TCMSP数据平台筛选出黄芪中的有效成分和相关靶标,使用GeneCards、OMIM网站数据库在线搜索出DNP的疾病相关靶标,取疾病和药物相同靶标交集,再利用Cytoscape 3.8.2构建药物-效应成分-疾病-靶标相互作用网络,进行拓扑学分析;从Uniprot数据库中获取靶点蛋白的基因名称,利用STRING在线数据库进行靶点蛋白与蛋白互作(Protein-protein interaction,PPI)网络分析;再进行GO功能分析和KEGG通路功能富集分析,推断黄芪减少DNP的机制是否和Akt1/mTOR自噬通路相关,再利用黄芪干预糖尿病肾病动物模型探讨其作用机制是否和预测的一致。结果黄芪中20种核心化合物有作用靶点174个,DNP相关靶标有1862个,交集靶标有98个,关键效应分子有10个。PPI图显示黄芪发挥效应的目标蛋白主要是AKT1、VEGFA、IL6、CASP3、MAPK1、JUN等。GO分析黄芪药效主要与细胞因子受体结合及其活性、核受体活性、转录因子活性等有关,KEGG分析表明黄芪药效基础主要作用与糖尿病并发症中AGE-RAGE、MAPK、PI3K-Akt等信号通路有关。动物实验显示黄芪能明显改善糖尿病肾病的大鼠的肾功能,尤其改善蛋白尿指标,通过上调足细胞Nephrin蛋白保护了肾小球滤过屏障,减少了蛋白尿的产生(P<0.05),同时下调了Akt1、总mTOR及其mRNA表达(P<0.05),从而增强了肾足细胞的自噬活性,也起到减少DNP的作用。结论网络药理分析显示黄芪可能通过多靶点效应发挥减少DNP作用,潜在的分子机制和Akt1/mTOR自噬通路有关,再经过实验研究说明Akt1/mTOR自噬通路是黄芪减少糖尿病肾病蛋白尿作用机制之一。
Objective To explore the mechanism of Radix Astragali seu Hedysari in reducing diabetic nephropathy proteinuria(DNP)through the analysis of network pharmacology and related animal experiments.Methods The TCMSP data platform was used for screening out the effective components and related targets in Radix Astragali seu Hedysari.GeneCards and OMIM website databases were used for searching for disease-related targets of DNP online,selecting the intersection of the same target of disease and drug.And then Cytoscape 3.8.2 was used for constructing a"drug-effectordisease-target"interaction network and Topological analysis;The Uniprot database was used for obtaining the gene name of the target protein,and the STRING online database was used for performing network analysis of the proteinprotein interaction(PPI)of the target protein;then GO function analysis and KEGG pathway function enrichment analysis was performed to infer whether the mechanism of Radix Astragali seu Hedysari reducing DNP is related to the Akt1/mTOR autophagy pathway,and then we used Radix Astragali seu Hedysari to intervene in the experiment of diabetic nephropathy animal model to explore whether its mechanism of action is consistent with the prediction.Results The 20 core compounds in Radix Astragali seu Hedysari had 174 action targets,1862 DNP-related targets,98 intersection targets,and 10 key effector molecules.The PPI chart showed that the target proteins of Radix Astragali seu Hedysari were mainly AKT1,VEGFA,IL6,CASP3,MAPK1,JUN,etc.The results of GO analysis indicated that the medicinal effects of Radix Astragali seu Hedysari were mainly related to cytokine receptor binding and its activity,nuclear receptor activity,transcription factor activity,etc.The results of KEGG indicated that the main effects of Radix Astragali seu Hedysari were related to AGE-RAGE,MAPK,AGE-RAGE,MAPK,and other factors in diabetic complications.PI3 K-Akt and other signal pathways were related.Animal experiments showed that Radix Astragali seu Hedysari can significantly impr
作者
姚琼
叶太生
张莹雯
王秀萍
彭艳芳
柯浩亮
Yao Qiong;Ye Taisheng;Zhang Yingwen;Wang Xiuping;Peng Yanfang;Ke Haoliang(Medical College of Jianghan University,Wuhan 430056,China;Department of Traditional Chinese Medicine,Zhongnan Hospital of Wuhan University,Wuhan 430071,China)
出处
《世界科学技术-中医药现代化》
CSCD
北大核心
2021年第8期2699-2710,共12页
Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology
基金
湖北省自然科学基金委员会面上项目(2019CFB710):基于miRNA调控自噬的当归补血汤治疗糖尿病肾病的作用机制研究,负责人:叶太生
国家自然科学基金委员会面上项目(81373793):当归补血汤调控内质网应激治疗糖尿病肾病的机制研究,负责人:张莹雯
2020年度武汉大学中南医院科研创新平台建设支撑项目(PTXM2021034):当归补血汤延缓2型糖尿病肾病进展的临床研究,负责人:叶太生
关键词
黄芪
糖尿病肾病蛋白尿
网络药理学
Akt1/mTOR
自噬
Radix Astragali seu Hedysari
Diabetic nephropathy proteinuria
Network pharmacology
Akt1/mTOR
Autophagy
