基于UPLC-Q-TOF-MS/MS的芪参益气滴丸体内成分鉴定及作用机制研究

Identification of in vivo components and exploration of the mechanism of action of Qishen Yiqi Dripping Pills based on UPLC-Q-TOF-MS/MS

关键词:  芪参益气滴丸  UPLC-Q-TOF-MS/MS  体内成分鉴定  心肌能量代谢

Key words:  Qishen Yiqi Dripping Pills  UPLC-Q-TOF-MS/MS  in vivo component identification  myocardial energy metabolism

摘要:

[目的] 基于超高效液相色谱-四极杆-飞行时间质谱（UPLC-Q-TOF-MS/MS）技术，系统鉴定芪参益气滴丸在大鼠血清与心脏组织中的入血/入心成分，解释其通过能量代谢相关信号通路发挥心肌保护作用的潜在机制。[方法] 采用UPLC-Q-TOF-MS/MS分析芪参益气滴丸灌胃后大鼠血清及心脏组织样本，通过高分辨天然产物数据库及文献比对确认化合物结构。结合近年心肌能量代谢文献研究，从能量底物利用、线粒体功能、嘌呤循环与氧化还原稳态等通路，探讨入血/入心成分的能量调控作用。[结果] 共鉴定出血清中12个化合物及心脏组织中9 个化合物，主要包括11 个氨基酸类、2个脂肪酸类、3个酚酸类、1个黄酮类、2 个嘌呤类、1个酰胺类、1 个庚烷类。[结论] 芪参益气滴丸可能通过“多成分-多通路-多环节”协同调控腺苷酸活化蛋白激酶（AMPK）-雷帕霉素机械靶蛋白（mTOR）-去乙酰化酶1（SIRT1）、AMPK-核因子E2相关因子2（Nrf2）-PTEN诱导激酶1（PINK1）/E3泛素蛋白连接酶（Parkin）、三羧酸循环（TCA）补偿及Nrf2-核因子-κB（NF-κB）等关键能量代谢网络，从而改善心肌能量失衡，为阐明其药效物质基础提供实验依据。

Abstract:

[Objective] This study employed ultra- performance liquid chromatography coupled with quadrupole time- of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）to systematically identify the absorbed constituents of Qishen Yiqi Dripping Pills（QSYQ）in rat serum and myocardial tissue，and to elucidate the potential cardioprotective mechanisms through energy metabolism-related signaling pathways. [Methods] UPLC-Q-TOF-MS/MS was used to analyze serum and myocardial tissue samples from rats administered QSYQ. The chemical structures of the detected compounds were confirmed through high-resolution natural product databases and literature comparison. Based on recent literature on myocardial energy metabolism，the study explored the energy-regulating effects of the absorbed constituents，focusing on pathways related to energy substrate utilization，mitochondrial function，purine cycling，and redox homeostasis. [Results] A total of 12 compounds were identified in serum and 9 in myocardial tissue，primarily including 11 amino acids，2 fatty acids，3 phenolic acids，1 flavonoid，2 purine derivatives，1 amide，and 1 heptane. [Conclusion] QSYQ may exert its cardioprotective effects through a“multi-component，multi-pathway，and multi-target”synergistic regulation of key energy metabolism networks，such as AMPK-mTOR-SIRT1，AMPK-Nrf2-PINK1/Parkin，TCA anaplerosis，and Nrf2-NF-κB pathways，thereby improving myocardial energy imbalance. This provides experimental evidence supporting the material basis for its pharmacological effects.