基于UHPLC-Q-Exactive Orbitrap MS和网络药理学探讨益气祛风方治疗糖尿病肾病作用机制

[目的] 借助超高效液相色谱-四级杆静电场轨道阱质谱仪（UHPLC-Q-Exactive Orbitrap MS）技术结合网络药理学和分子对接技术,分析益气祛风方防治糖尿病肾病（DN）的物质基础和作用机制。[方法] 采用UHPLC-Q-Exactive Orbitrap MS鉴定益气祛风方的主要化学成分,采用网络药理学方法构建“主要成分-核心靶点-信号通路”网络,进行基因本体（GO）功能富集分析和京都基因与基因组百科全书（KEGG）通路富集分析,对主要活性成分与核心靶点进行分子对接。[结果] 从益气祛风方共鉴定出115个化学成分,获得40个核心靶点,主要涉及磷脂酰肌醇-3激酶-蛋白激酶B（PI3K-Akt）信号通路、脂质及动脉硬化、糖基化终产物及受体（AGE-RAGE）信号通路、趋化因子信号通路及低氧诱导因子（HIF）1信号通路等。分子对接结果表明生松素、荠苧黄酮、槲皮素、N-乙酰多巴胺二聚体-1、N-乙酰多巴胺二聚体-2等成分与部分核心靶点有较好的结合活性。[结论] 本研究初步鉴定了益气祛风方治疗DN潜在的有效成分并预测了其作用靶点,为进一步研究中医“从风论治”法和益气祛风方治疗糖尿病肾病的作用机制提供了新的思路。

Mechanism of Yiqi Qufeng Formula in the treatment of diabetic nephropathy based on UHPLC-Q-Exactive Orbitrap MS and network pharmacology

[Objective] To analyze the material basis and mechanism of Yiqi Qufeng Formula(YQQF) in the prevention and treatment of diabetic nephropathy(DN) by means of ultra-high performance liquid chromatography-quadrupole electrostatic field orbitrap mass spectrometry(UHPLC-Q-Exactive Orbitrap MS) combined with network pharmacology and molecular docking technology. [Methods] The main chemical components of YQQF were identified by UHPLC-Q-Exactive Orbitrap MS, and the "main component-core target-signal pathway" network was constructed by network pharmacology. GO functional enrichment analysis and KEGG pathway enrichment analysis were conducted, and molecular docking between the main active components and core targets was conducted. [Results] A total of 115 chemical components were identified from YQQF and 40 core targets were obtained, mainly involving PI3K-Akt signaling pathway, lipid-arteriosclerosis, AGE-RAGE signaling pathway, chemokine signaling pathway and HIF-1 signaling pathway. Molecular docking results showed that pinocembrin, mosloflavone, quercetin, N-acetyldopamine dimer-1, N-acetyldopamine dimer-2 and other components had good binding activity with some core targets. [Conclusion] This study preliminarily identified the potential effective components of YQQF, providing ideas for further research on the "wind-based treatment" method and the mechanism of YQQF.