基于网络药理学探讨胡芦巴丸化裁方治疗糖尿病肾病的作用机制

目的利用网络药理学方法探讨胡芦巴丸化裁方治疗糖尿病肾病的作用机制。方法利用TCMSP数据库和BATMAN-TCM数据库筛选得到胡芦巴丸化裁方的有效成分及相关作用靶点,并运用UniProt数据库和SwissTargetPrediction数据库对靶点信息进行矫正和补充;使用GeneCards数据库、TTD数据库、OMIM数据库和DrugBank数据库获得糖尿病肾病的疾病相关靶点;利用在线作图工具Jvenn获得胡芦巴丸化裁方与糖尿病肾病的共同靶点;运用String11.0构建蛋白相互作用(PPI)网络,对网络图中的关键靶蛋白进行筛选和分析;运用cytoscape3.8.0构建"药物—成分—疾病—靶点"网络图,并对主要活性成分进行分析;利用DAVID 6.8数据库对胡芦巴丸化裁方和糖尿病肾病共同靶点进行基因本体论(GO)富集分析和京都基因与基因组百科全书(KEGG)富集分析,对共同靶点的生物过程及主要代谢通路进行讨论。结果经过筛选去重得到胡芦巴丸化裁方的有效活性成分55个,药物作用靶点538个,糖尿病肾病疾病靶点6971个;利用Jvenn取交集得到药物—疾病共同靶点413个;GO富集分析显示这些靶点涉及对药物的反应、对缺氧的反应、炎症反应、信号转导等生物学过程,KEGG富集分析显示共同靶点所富集的通路包括PI3K-Akt信号通路、胰岛素抵抗、钙离子信号通路、TNF信号通路等。结论胡芦巴丸化裁方对于DKD的治疗具有多成分、多靶点、多通路的特点,有可能是通过胰岛素(INS)、蛋白激酶B1(AKT1)、肿瘤蛋白p53(TP53)、白介素-6(IL-6)等核心靶点对PI3K-Akt信号通路、钙离子信号通路、TNF信号通路等进行调控从而发挥治疗作用。

Study on the Mechanism of Modified Huluba Pill Formula in Treating Diabetic Kidney Disease Based on Network Pharmacology

Objective To explore the mechanism of Modified Huluba Pill Formula in treating diabetic kidney disease(DKD)by means of network pharmacology.Methods The effective components and related targets of Modified Huluba Pill Formula were screened by the TCMSP database and BATMAN-TCM database,and the Uni Prot database and SwissTargetPrediction database were used to correct and supplement the target information,respectively.The disease related targets of DKD were obtained by using the GeneCards database,TTD database,OMIM database and DrugBank database.The common targets of Modified Huluba Pill Formula and DKD were obtained by the Jvenn,an online mapping tool.The protein-protein interaction(PPI)network was constructed by String11.0,and the key target proteins in the network map were screened and analyzed.The cytoscape3.8.0 was used to construct the"drug-component-disease-target"network map and analyze the main active components.The common target of Modified Huluba Pill Formula and DKD was analyzed by gene ontology(GO)enrichment analysis and kyoto encyclopedia of gene and genome(KEGG)enrichment analysis using DAVID 6.8,the biological process and main metabolic pathways of the common target were discussed.Results Totally 55 effective active components and 538 drug targets of Modified Huluba Pill Formula,6971 DKD targets were obtained after screening and deduplication.Four hundred and thirteen drug-disease common targets were obtained by Jvenn.GO enrichment analysis showed that these targets were involved in biological processes such as response to drug,response to hypoxia,in?ammatory response,signal transduction,etc.KEGG enrichment analysis showed that the pathways enriched by common targets included PI3 K-Akt signaling pathway,insulin resistance,calcium signaling pathway,TNF signaling pathway and so on.Conclusion Modified Huluba Pill Formula has the characteristics of multi-components,multi-targets and multi-pathways in the treatment of DKD,which may play a therapeutic role by regulating PI3 K-Akt signaling pathway,calcium signaling pathway and TNF signaling pathway through the intervention of insulin(INS),protein kinase B1(AKT1),tumor protein P53(TP53),interleukin 6(IL-6)and other core targets.