基于网络药理学和分子对接的丹参酮ⅡA治疗糖尿病肾病的机制研究

Mechanism study of tanshinone ⅡA in treatment of diabetic nephropathy based on network pharmacology and molecular docking

目的 基于网络药理学和分子对接的方法研究丹参酮ⅡA治疗糖尿病肾病的分子的机制。方法 利用Swiss Target Prediction、TCMSP、PharmMapper、GeneCards平台预测丹参酮ⅡA的作用靶点,从OMIM、DrugBank、TTD、GeneCards数据库中筛选获得糖尿病肾病的相关靶点。将得到的丹参酮ⅡA的作用靶点与疾病靶点取交集得到潜在靶点,构建蛋白质相互作用(PPI)网络,并通过网络拓扑分析筛选核心靶点。采用Metascape平台分析对交集靶点进行基因本体(GO)功能富集分析与京都基因与基因组百科全书(KEGG)通路富集分析。最后运用AutoDock Vina 1.1.2对丹参酮ⅡA和核心靶点之间进行分子对接验证。结果 共筛选出96个丹参酮ⅡA调控糖尿病肾病的潜在靶点,通过网络拓扑分析中的度(degree)值筛选出白蛋白(ALB)、蛋白激酶B1(AKT1)、白细胞介素-6(IL-6)、血管内皮生长因子(VEGFA)、肿瘤坏死因子(TNF)、肿瘤蛋白p53(TP53)、丝裂原激活蛋白激酶8(MAPK8)、胱天蛋白酶3(CASP3)8个核心靶点;GO富集分析筛选出活性氧代谢过程、细胞迁移的正向调节、氧化应激反应、细胞死亡的正向调节等20个生物学过程,KEGG富集筛选出流体剪切应力和动脉粥样硬化通路、肿瘤坏死因子信号通路、叉头转录因子(FoxO)信号通路、VEGF等20条通路。分子对接验证结果显示,核心靶点与丹参酮ⅡA之间均有良好的结合活性。结论 本研究表明丹参酮ⅡA可能通过多靶点、多通路调控糖尿病肾病。

Objective To study the molecular mechanism of tanshinone ⅡAin treatment of diabetic nephropathy based on bioinformatics and molecular docking methods. Methods The Swiss Target Prediction, TCMSP, PharmMapper, and GeneCards platforms were used to predict the target of tanshinone ⅡA, and the relevant targets of diabetic nephropathy were screened from OMIM,DrugBank, TTD, and GeneCards databases. Target of tanshinone ⅡAwas intersected with the disease target to obtain potential target,and the protein interaction(PPI) network was constructed, and the core target was screened by network topology analysis. Metascape platform was used for gene ontology(GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis for intersection targets. Finally, AutoDock Vina 1.1.2 was used to verify the molecular docking between tanshinone ⅡAand the core target. Results A total of 96 potential targets of tanshinone ⅡAregulating diabetic nephropathy were selected. Albumin(ALB), protein kinase B1(AKT1), interleukin 6(IL-6), vascular endothelial growth factor(VEGFA), tumor necrosis factor(TNF), tumor protein p53(TP53), mitogen-activated protein kinase 8(MAPK8) and cysts were screened by degree value in network topology analysis 8 core targets of protease 3(CASP3). GO enrichment analysis screened out 20 biological processes,including active oxygen metabolism, positive regulation of cell migration, oxidative stress response, and positive regulation of cell death. KEGG enrichment screened 20 pathways including fluid shear stress and atherosclerosis pathway, tumor necrosis factor signaling pathway, FoxO signaling pathway and VEGF pathway. The results of molecular docking showed that the core target had good binding activity with tanshinone ⅡA. Conclusion This study suggests that tanshinone ⅡAmay regulate diabetic nephropathy through multi-target and multi-pathway.