基于系统药理学研究黄芪-熟地黄治疗糖尿病肾病的作用机制

The action mechanism of Huangqi-Shu Dihuang medicine pair on diabetic nephropathy based on system pharmacology

目的:基于系统药理学分析黄芪-熟地黄药对治疗糖尿病肾病的作用机制。方法:在中药系统药理学一体化分析数据库(TCMSP)中分别查询黄芪-熟地黄药对中所包含的有效化学成分;利用PubChem数据库查找黄芪-熟地黄中所筛化合物的结构式以及该化合物的SMILES,再通过Swiss Target Prediction、DrugBank数据库预测其靶点;通过DisGeNET、GeneCards数据库挖掘并筛选与糖尿病肾病相关性评分高的作用靶点,并构建“黄芪-熟地黄”所作用的蛋白/基因之间相互作用网络图、化合物与靶点相互作用的网络图以及药物-靶点-通路网络图;通过David数据库对“黄芪-熟地黄”药对作用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)分析。结果:经过TCMSP数据库药物代谢动力学筛选得到“黄芪-熟地黄”药对活性成分20个,活性成分靶点651个;作用于糖尿病肾病的靶点139个;通过GO分析得到50个生物学过程、33个细胞组成和35个分子功能;经KEGG分析得到30条信号通路包括肿瘤坏死因子(Tumor Necrosis Factor,TNF)信号通路、血管内皮生长因子(Vascular Endothelial Growth Factor,VEGF)信号通路等。结论:本研究结果一定程度上诠释了“黄芪-熟地黄”药对可以降低微量白蛋白尿、炎症反应、缺氧介导等相关通路发挥治疗糖尿病肾病在中医层面的意义,以上结论尚不能作为临床疗效的依据,有待相关基础药理学和临床研究进一步验证。

Objective: To analyze the action mechanism of Huangqi(Astragalus)-Shu Dihuang(Rehmannia glutinosa)medicine pair on diabetic nephropathy based on system pharmacology. Methods: The effective chemical components contained in Huangqi-Shu Dihuang medicine pair were searched by TCMSP. The structural formula and SMILES of the compound of Huangqi-Shu Dihuang medicine pair were searched by Pub Chem, and then its targets were predicted by Swiss Target Prediction and Drug Bank databases. Through Dis Ge NET and Gene Cards databases, the targets with high correlation scores with diabetic nephropathy were mined and screened. The protein-gene interaction network diagram and the network diagram of the interaction between compounds and targets of Huangqi-Shu Dihuang medicine pair were constructed by Dis Ge NET and Gene Cards databases. The GO enrichment analysis and KEGG pathway enrichment analysis were performed on the targets of Huangqi-Shu Dihuang medicine pair by David database. Results: After pharmacokinetic screening in TCMSP database, there were 20 active ingredients and 651 active ingredient targets of Huangqi-Shu Dihuang medicine pair, with 139 targets acting on diabetic nephropathy. A total of 50 biological processes, 33 cellular components, and 35 molecular functions were obtained by the GO enrichment analysis. The KEGG analysis obtained 30 signaling pathways including TNF signaling pathway, VEGF signaling pathway and so on. Conclusion: The results of this study interpret the significance of Huangqi-Shu Dihuang medicine pair to a certain extent in treating diabetic nephropathy by reducing microalbuminuria, inflammatory response, hypoxiamediated and other related pathways. However, the above conclusion cannot be used as the basis for clinical efficacy, it remains to be further validated by relevant basic pharmacology and clinical studies.