Background

Danqi Tongmai tablet (DQTM), a combination of salvianolic acids (SA) and panax notoginsenosides (PNS), is now in phase II clinical trial developed for the treatment of cardiovascular diseases. However, the mechanisms of its protective effects through regulating endogenous metabolites remain unclear.

Purpose

The purpose of this study was to explore the protective effects of DQTM on acute myocardial ischemia rats by comprehensive metabolomics profiling.

Study design

The rats were divided into three groups: sham-operating, acute myocardial ischemia (AMI) and DQTM groups. The plasma and heart were collected and profiled by LC-MS based metabolomics and lipidomics. Based on the identified differential metabolites, the pathway analysis results were obtained and further validated using the network pharmacology approach.

Methods

The AMI model was induced by ligating the left anterior descending coronary artery. The metabolomics and lipidomics profiling were based on two established LC–QTOF/MS analysis methods. The raw data were processed using XCMS Online, then the differential metabolites with nonparametric t-test p value less than 0.05 were selected and identified using HMDB and METLIN. The pathway analysis was conducted using MetaboAnalyst and validated with the predicted network results obtained by BATMAN-TCM.

Results

The metabolomics and lipidomics profiles of plasma and heart in response to AMI and DQTM were significantly different. The AMI operation had a serious influence on metabolites in heart ischemia region, while DQTM had a greater impact on lipids in heart non-ischemia region. A total of 151 differential metabolites were identified, including mainly amino acids and fatty acids. Multiple metabolic pathways were disturbed after AMI and could be restored by DQTM, of which arachidonic acid metabolism was further validated with the predicted results of network pharmacology.

Conclusion

The protective effects of DQTM on acute myocardial ischemia rats could be achieved through the regulation of multiple metabolic pathways.

中文翻译：

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综合代谢组学分析探讨丹芪通脉片对急性心肌缺血大鼠的保护作用。

背景

丹参通脉片（DQTM）是丹酚酸（SA）和三七总皂甙（PNS）的组合，目前处于用于治疗心血管疾病的II期临床试验中。然而，其通过调节内源性代谢产物的保护作用的机制尚不清楚。

目的

本研究的目的是通过综合代谢组学分析来探讨DQTM对急性心肌缺血大鼠的保护作用。

学习规划

将大鼠分为三组：假手术组，急性心肌缺血（AMI）和DQTM组。收集血浆和心脏，并通过基于LC-MS的代谢组学和脂质组学进行分析。基于鉴定出的差异代谢物，获得通路分析结果，并使用网络药理学方法进一步验证。

方法

通过结扎左冠状动脉前降支来诱发AMI模型。代谢组学和脂质组学分析基于两种已建立的LC–QTOF / MS分析方法。使用XCMS Online处理原始数据，然后使用HMDB和METLIN选择非参数t检验p值小于0.05的差异代谢物。使用MetaboAnalyst进行路径分析，并通过BATMAN-TCM获得的预测网络结果进行验证。

结果

血浆和心脏对AMI和DQTM的代谢组学和脂质组学特征存在显着差异。AMI操作对心脏缺血区域的代谢产物有严重影响，而DQTM对心脏非缺血区域的脂质影响更大。总共鉴定出151种差异代谢物，主要包括氨基酸和脂肪酸。AMI后多个代谢途径受到干扰，可以通过DQTM恢复，其中花生四烯酸的代谢作用已通过网络药理学的预测结果得到了进一步验证。

结论

DQTM对急性心肌缺血大鼠的保护作用可以通过多种代谢途径的调节来实现。