基于UPLC-Q/TOF-MS和网络药理学分析丹参川芎嗪注射液入脑成分及作用机制

Analysis of Brain Components and Mechanism of Danshen Ligustrazine Injection Based on UPLC-Q/TOF-MS and Network Pharmacology

目的建立超高效液相色谱与四极杆-飞行时间串联质谱联用技术(UPLC-Q/TOF-MS)分析丹参川芎嗪注射液的入脑成分检测方法,并运用网络药理学的方法研究注射液入脑成分发挥作用的机制。方法采用UPLC-Q/TOF-MS技术,定性分析该制剂进入大鼠脑内的原型成分。运用TCMSP、DAVID等数据库对入脑成分的潜在靶点和作用通路进行预测,通过Cytoscape软件构建入脑成分-潜在靶点-作用通路网络。结果在大鼠给药脑组织中共鉴定出7种入脑成分,涉及98个作用靶点,作用于cGMP-PKG信号通路及钙信号通路等10条通路。结论该实验应用UPLC-Q/TOF-MS技术,建立一种快速、可靠的分析丹参川芎嗪注射液入脑成分的方法,并通过网络药理学方法,研究入脑成分的作用机制,初步揭示了注射液在脑内的药效物质基础,阐明了注射液在脑内的作用机制。

OBJECTIVE To establish a method for determination of the components in Danshen Ligustrazine Injection which can penetrate into brain by ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry(UPLC-Q/TOF-MS), and explore the mechanism of action by network pharmacology. METHODS UPLC-Q/TOF-MS technique was used to qualitatively analyze the prototype components penetrating into the brain of rats. TCMSP, DAVID and other databases were used to predict the targets and biological pathways of the components, and the brain component-target-biological pathway network was constructed by Cytoscape software. RESULTS Seven kinds of components were identified in the brain tissue of rats, involving 98 targets, which acted on 10 pathways including cGMP-PKG signaling pathway and calcium signaling pathway. CONCLUSION UPLC-Q/TOF-MS technique is a rapid and reliable method for analyzing the components penetrating into brain of Danshen Ligustrazine Injection. The mechanism of action and pharmacodynamic substances of the injection for the pharmacological effects in brain were preliminarily clarified by network pharmacology method.