基于网络药理学和体内实验探究黄蜀葵花总黄酮治疗急性肾损伤的分子机制  

Molecular Mechanism of Total Flavonoids of Abelmoschus manihot in Treatment of AKI Based on Network Pharmacology and in vivo Experiment

作　　者：詹倩 王富江 葛海涛 ZHAN Qian;WANG Fujiang;GE Haitao(Nanjing University of Chinese Medicine,Nanjing 210023,China;Suzhong Pharma,Nanjing 211899,China)

机构地区：[1]南京中医药大学,江苏南京210023 [2]江苏苏中药业研究院有限公司,江苏南京211198

出　　处：《中医药信息》2022年第9期18-25,共8页Information on Traditional Chinese Medicine

基　　金：南京中医药大学校企联合项目(XZR2020099)。

摘　　要：目的:基于网络药理学及体内实验探究和验证黄蜀葵花总黄酮治疗急性肾损伤的作用靶点及信号通路。方法:从中国知网和PubChem数据库中检索黄蜀葵花总黄酮成分及相关信息;通过Swiss Target Prediction数据库和中药系统药理学数据库与分析平台(TCMSP)数据库获得药物靶点;通过GeneCards、Disgenet数据库和ImageGP平台收集急性肾损伤相关的疾病靶点,选取与药物靶点重复的靶点作为交集靶点;利用STRING数据库和Cytoscape 3.8.0软件构建PPI网络,筛选核心靶点;使用DAVID数据库进行基因本体(gene ontology,GO)富集分析和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路注释分析。采用尾静脉注射阿霉素的方法建立急性肾损伤小鼠模型,通过苏木精-伊红(HE)和过碘酸雪夫(PAS)染色观察组织病理变化,通过免疫组织化学法(IHC)进行靶点验证。结果:网络药理学分析显示,黄蜀葵花总黄酮可能通过STAT3、AKT1、MAPK1、TP53、PIK3CA、JUN、TNF、VEGFA和EGFR等靶点,参与MAPK级联激活、凋亡过程负调控和细胞增殖正调控等生物过程,通过Toll样受体信号通路、HIF-1信号通路、TNF信号通路以及PI3K/Akt信号通路等途径治疗急性肾损伤。动物实验结果显示,与模型组比较,给药组肾脏组织病理损伤得到改善;肾脏组织中Akt蛋白表达水平显著升高(P<0.01),MAPK蛋白表达水平显著降低(P<0.05)。结论:黄蜀葵花总黄酮可能通过影响Akt、MAPK的表达,减轻阿霉素诱导小鼠产生的肾损伤。Objective:To explore the action targets and signaling pathways of total flavonoids of Abelmoschus manihot in treatment of acute kidney injury(AKI)based on network pharmacology and in vivo experiment.Methods:The components and related information of total flavonoids in Abelmoschus manihot were retrieved from the databases of CNKI and PubChem.The drug targets were obtained through the databases of Swiss Target Prediction,Chinese medicinal systems pharmacology and TCMSP.The AKI-related disease targets were collected through the GeneCards and Disgenet databases,and the ImageGP platform was used to obtain the intersection targets of the total flavonoids and AKI.With the help of Cytoscape 3.8.0 software and STRING database,PPI network was constructed to screen core targets.GO enrichment analysis and KEGG pathway were annotated and analyzed by using DAVID database.AKI mice model was established by a single tail intravenous injection of Adriamycin.HE staining and PAS staining were used to observe the pathological changes of kidneys in mice,and ICH method was used to verify the targets.Results:Network pharmacology analysis showed that the total flavonoids of Abelmoschus manihot could treat AKI by acting on the targets of STAT3,AKT1,MAPK1,TP53,PIK3CA,JUN,TNF,VEGFA and EGFR,involving in biological processes such as MAPK cascade,negative regulation of apoptotic process and positive regulation of cell proliferation,and participating in pathways,including toll-like receptor signaling pathway,HIF-1 signaling pathway,TNF signaling pathway and PI3K/Akt signaling pathway,in treatment of AKI.The results of animal experiments showed that compared with those in the model group,the pathological damage of renal tissues was improved,the expression level of Akt in renal tissues was significantly increased(P<0.01),and the expression level of MAPK was significantly reduced in the medication group(P<0.05).Conclusion:The total flavonoids of Abelmoschus manihot may reduce Adriniamycin-induced renal injury by regulating the expressions of Akt

关 键 词：黄蜀葵花 总黄酮 急性肾损伤 网络药理学 分子机制 

分 类 号：R285.5[医药卫生—中药学]