Nan Lyu, Peng Lai, Jinxia Zhao, Mengzhe Guo, Jun Liang, Haibo Wang, Houfa Geng
Clinical College, Xuzhou Medical University, Xuzhou Central Hospital, Xuzhou, China.
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China.
Front Pharmacol. 2021 Oct 27;12:731734. doi: 10.3389/fphar.2021.731734. eCollection 2021.
As current clinical practice guidelines, ticagrelor is the suggested therapeutic scheme to prevent adverse cardiovascular events in acute myocardial infarction (AMI) patients undergoing percutaneous coronary intervention (PCI) treatment. However, this therapeutic strategy still fails, and around 30% patients display inadequate antiplatelet responses. Musk Tongxin Dripping Pill (MTDP) in Chinese hospital was usually considered as the combination with ticagrelor to improve the treatment effect. Unfortunately, the mechanism has not been elucidated. The untargeted metabolomic method was introduced based on liquid chromatography-high-resolution mass spectrometry (HPLC-HRMS) coupled with STI for the research of the drug combination mechanism between ticagrelor and MTDP. 28 patients with a confirmed diagnosis of AMI were selectively collected, who were then divided into two different dosage regimen groups, and the serum samples were collected for the untargeted metabolomics assay. Then the differential metabolites were associated with blood biochemical indicators. The GLS values in both groups increased after treatment and those in the ticagrelor and MTDP combination group after treatment were higher than those in the ticagrelor group ( < 0.05), suggesting that the combination medication has better therapeutic effect on patients with myocardial infarction. From metabolomics analysis, the species of metabolites changed in two groups before and after treatment. Moreover, 93 differential metabolites changed in the drug combination group compared with the ticagrelor group after treatment ( < 0.05), which mainly related to changes in fatty acid metabolism pathways. Then the differential metabolites were found to be related with blood biochemical indicators, such as lipid, high-density lipoprotein (HDL), and low-density lipoprotein (LDL). This work will provide a possible mechanism of the drug combination interaction between ticagrelor and MTDP from two angles of echocardiography and metabonomics. Several potential metabolic pathways were also found to have a relationship with MTDP, which will provide a new perspective in clinical medication.
作为当前的临床实践指南，替格瑞洛是接受经皮冠状动脉介入治疗（PCI）的急性心肌梗死（AMI）患者预防不良心血管事件的推荐治疗方案。然而，这种治疗策略仍然存在不足，约30%的患者表现出抗血小板反应不足。在中国医院，麝香通心滴丸（MTDP）通常被认为可与替格瑞洛联合使用以提高治疗效果。遗憾的是，其机制尚未阐明。基于液相色谱 - 高分辨率质谱（HPLC - HRMS）结合STI引入非靶向代谢组学方法，用于研究替格瑞洛与MTDP的药物联合作用机制。选择性收集了28例确诊为AMI的患者，将其分为两个不同剂量方案组，并采集血清样本进行非靶向代谢组学分析。然后将差异代谢物与血液生化指标相关联。两组治疗后的GLS值均升高，且替格瑞洛与MTDP联合治疗组治疗后的GLS值高于替格瑞洛组（<0.05），表明联合用药对心肌梗死患者具有更好的治疗效果。从代谢组学分析来看，两组治疗前后代谢物种类发生了变化。此外，治疗后药物联合组与替格瑞洛组相比有93种差异代谢物发生变化（<0.05），主要与脂肪酸代谢途径的变化有关。然后发现差异代谢物与血液生化指标如血脂、高密度脂蛋白（HDL）和低密度脂蛋白（LDL）相关。这项工作将从超声心动图和代谢组学两个角度为替格瑞洛与MTDP的药物联合相互作用提供一种可能的机制。还发现了几个潜在的代谢途径与MTDP有关，这将为临床用药提供新的视角。
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