摘要
目的探究浙贝母-金银花药对治疗糖尿病足的作用机制。方法通过TCMSP筛选浙贝母-金银花药对的药物成分, 使用Swiss Target Prediction预测药物成分的作用靶点, 运用GeneCards获取糖尿病足的疾病靶点, 利用Venny 2.1获取交集靶点。使用STRING进行蛋白质间作用网络(PPI)分析并使用Cytoscape构建网络图, 利用Metascape进行基因本体(GO)及京都基因和基因组百科全书(KEGG)分析。使用Cytoscape软件构建"药物-靶点-通路"网络图。建立糖尿病足大鼠模型并用浙贝母-金银花药对局部外敷治疗患处, 观察治疗效果及检测血清筛选靶点表达。结果浙贝母-金银花药对中的38个有效成分通过多条通路直接作用于339个疾病靶点治疗糖尿病足, 其中木犀草素(Luteolin)、苦叶草素(Picropodophyllin)、天竺葵素(Pelargonidin)、紫鄂贝碱(Ziebeimine)、浙贝乙素(Peiminine)、腺苷(Adenosine)等是核心成分, TP53、EP300、HSP90AA1、CTNNB1、Akt1是至关重要的靶点。基因功能注释分析结果显示, 交集基因最可能相关的生物过程主要涉及细胞转录因子结合、细胞对氮化合物反应、激素反应等, 细胞组分主要涉及膜筏、质膜筏、小窝等, 分子功能主要涉及蛋白激酶活性、磷酸激酶活性、激酶活性等。通路富集分析结果提示浙贝母-金银花药对主要参与PI3K/AKT、HIF-1、EGFR、MAPK等信号通路。浙贝母-金银花药对修复糖尿病足鼠模型的病变部位的效果明显, 且血清TP53、EP300、HSP90AA1、CTNNB1、Akt1蛋白表达明显增加。结论浙贝母-金银花药对治疗糖尿病足的机制是通过调节PI3K/AKT、HIF-1、EGFR、MAPK等信号通路的TP53、EP300、HSP90AA1、CTNNB1、Akt1等疾病靶点, 进而调节酶类活性、抗炎等生物过程。
Objective To explore the mechanism of the treatment of diabetic feet with thunberg fritillary and honeysuckle based on pharmacological and animal experiments.Methods The drug ingredients of the drug pair of thunberg fritillary and honeysuckle were obtained from TCMSP,and the targets of the drug pair were obtained from the Swiss target prediction.The targets of the disease target of diabetic foot were screened.The cross target was obtained using Venny 2.1.A protein-protein interaction(PPI)network was constructed by STRING and Cytoscape software.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were carried out by Metascape.The ingredient-target-pathway network was established by Cytoscape software.The diabetic foot rat model was established,and the effects of the treatment and the detection of serum screening targets were observed.Results The results show that 38 active ingredients in the drug pair acted on 339 disease targets to treat diabetic feet through multiple pathways.The core ingredients include luteolin,pelargonidinin,ziebeimine,peiminine,adenosine,and TP53,EP300,HSP90AA1,CTNNB1,and Akt1 are the critical targets.The results of the genetic function analysis show that the biological process is mainly involved in the combination of cellular transcription factors,the reaction of cells to nitrogen compounds,and hormone reactions.The main components of the cell component mainly involve the film raft,the membrane raft,the small space and so on.The molecular function mainly involves protein kinase activity,phosphate kinase activity,kinase activity and so on.The results of the KEGG enrichment analysis indicate the signaling pathways mainly include PI3K/AKT,HIF-1,EGFR,and MAPK.The local repair effect of the drug pair on the diabetic foot rat model is significant,and the expression of the serum TP53,EP300,HSP90AA1,CTNNB1,Akt1 is significantly increased.Conclusions The mechanism of the treatment of diabetes foot with thunberg fritillary and honeysuckle is mainly by regulating targets(TP53,EP300,HSP90AA1,CTNNB1 and Akt1),signal pathways(PI3K/AKT,HIF-1,EGFR and MAPK),and biological processes such as enzymatic activity and anti-inflammatory.
作者
霍磊
Huo Lei(Department of Surgery,the Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin 300250,China)
出处
《国际生物医学工程杂志》
CAS
2022年第2期130-135,共6页
International Journal of Biomedical Engineering
关键词
浙贝母-金银花药对
糖尿病足
网络药理学
作用机制
Thunberg fritillary and honeysuckle
Diabetic foot
Pharmacology
Mechanism of action
