基于网络药理学和分子对接的乾坤丹Ⅵ号治疗糖尿病肾脏疾病的机制研究

Study on the mechanism of Qiankundan Ⅵ in the treatment of diabetic kidney disease based on network pharmacology and molecular docking

关键词:  乾坤丹Ⅵ号  糖尿病肾脏疾病  网络药理学  分子对接  活性成分  靶点  信号通路

Key words:  Qiankundan Ⅵ  diabetic kidney disease  network pharmacology  molecular docking  active ingredient  target point  signal pathway

摘要:

[目的] 运用网络药理学研究方法探讨乾坤丹Ⅵ号防治糖尿病肾脏疾病（DKD）的作用机制。[方法] 基于TCMSP数据库获取乾坤丹Ⅵ号的化学成分及对应靶点，GeneCards、OMIM数据库检索DKD的疾病靶点；对药物与疾病靶点相映射得到乾坤丹Ⅵ号防治DKD的关键作用靶点，利用String数据库构建关键靶点的蛋白-蛋白相互作用（PPI）网络，运用Cytoscape软件筛选乾坤丹Ⅵ号防治DKD的核心靶点和功能模块，利用autodock软件对乾坤丹Ⅵ号的化学成分和核心蛋白进行分子对接。对关键靶点进行GO和KEGG通路富集分析，分析乾坤丹Ⅵ号对DKD的潜在作用机制。[结果] 得到乾坤丹Ⅵ号有效成分103种，靶点137个，预测靶点较多的成分有槲皮素、山柰酚、β-谷甾醇等，共得到关键靶点128个，分子功能模块6个。分子对接结果显示，乾坤丹Ⅵ号化学成分和靶点蛋白对接的平均结合能为-6.43 kcal/mol，其中槲皮素和PSGT2的结合能最高。GO和KEGG通路富集分析结果显示，乾坤丹Ⅵ号防治DKD与糖尿病并发症中的AGE-RAGE信号通路、Th17细胞分化、IL-17信号通路、钙信号通路、TNF信号通路、HIF-1信号通路等信号通路有关。[结论] 乾坤丹Ⅵ号通过多成分、多靶点、多信号通路的协同作用实现对DKD的防治作用，为乾坤丹Ⅵ号的进一步临床和实验研究提供了重要的科学依据。

Abstract:

[Objective] To explore the mechanism of Qiankundan Ⅵ in preventing and treating diabetic kidney disease (DKD) by the method of network pharmacology.[Methods] The chemical components and corresponding targets of Qiankundan Ⅵ were obtained based on TCMSP database,and disease targets of DKD were searched by GeneCards and OMIM database. The key action targets of Qiankundan Ⅵ for prevention and treatment of DKD were obtained by mapping drugs and disease targets. The protein-protein interaction (PPI) network of key targets was constructed by using String database. The core targets and functional modules of Qiankundan Ⅵ for prevention and treatment of DKD were screened by using Cytoscape software. The chemical components and core proteins of Qiankundan Ⅵ were linked by using autodock software. GO and KEGG pathway enrichment analysis was carried out on key targets,and the potential action mechanism of Qiankundan Ⅵ on DKD was analyzed.[Results] There were 103 kinds of effective components and 137 targets in Qiankundan Ⅵ. Quercetin,kaempferol,β-sitosterol and other components with more predicted targets were obtained,including 128 key targets and 6 molecular functional modules. The results of molecular docking showed that the average binding energy between the chemical components of Qiankundan Ⅵ and the target protein was-6.43 kcal/mol,and the binding energy between quercetin and PSGT2 was the highest. The results of GO and KEGG pathway enrichment analysis showed that the prevention and treatment of DKD by Qiankundan Ⅵ was related to the AGE-RAGE signal pathway,Th17 cell differentiation,IL-17 signal pathway,calcium signal pathway,TNF signal pathway and HIF-1 signal pathway in diabetic complications.[Conclusion] Qiankundan Ⅵ can prevent and treat DKD through the synergistic effect of multi-components,multi-targets and multi-signal pathways,which provides an important scientific basis for further clinical and experimental research of Qiankundan Ⅵ.