基于代谢组学的苦碟子注射液抗心肌缺血作用机制研究

目的明确苦碟子注射液对心脏组织的保护作用,探究其抗心肌缺血的作用机制。方法采用异丙肾上腺素(isoprenaline,ISO)建立大鼠心肌缺血模型,通过生化检测和病理组织切片研究,探究苦碟子注射液对心脏的保护作用;结合UPLC-Q-TOF/MS技术,对大鼠心脏组织和血浆样本进行无靶向代谢组学研究,获取ISO诱导心肌缺血的生物标志物和代谢通路。结果苦碟子注射液可改善心肌缺血模型大鼠心脏组织病理变化,显著降低大鼠血清天门冬氨酸氨基转移酶(aspartate transaminase,AST)、乳酸脱氢酶(lactate dehydrogenase,LDH)和血浆丙二醛(malondialdehyde,MDA)的含量。与对照组相比,筛选得到与心肌缺血密切相关的11个心脏生物标志物和10个血浆生物标志物,Metabo Analyst通路分析发现5条可能与心肌缺血相关的代谢通路。结论苦碟子注射液主要通过调控谷胱甘肽代谢、甘油磷脂代谢及亚麻酸代谢等通路起到预防心肌缺血的作用;不仅为阐明苦碟子注射液预防心肌缺血的作用机制提供依据,同时为苦碟子注射液的临床合理应用提供参考。

Mechanism of Kudiezi Injection against myocardial ischemia based on metabonomics in rats with myocardial ischemia

Objective To clarify the protective effect of Kudiezi Injection(苦碟子注射液)on cardiac tissue and explore its mechanism of anti-myocardial ischemia.Methods Isoproterenol(ISO)was used to establish the myocardial ischemia model in rats,and the protective effect of Kudiezi injection on the heart was studied by comparing biochemical tests and pathological tissue sections.In combination with UPLC-Q-TOF/MS,an untargeted metabolomics study was conducted on rat heart tissue and plasma samples to obtain biomarkers and metabolic pathways for ISO-induced dmyocardial ischemia.Results Kudiezi Injection improved the pathological changes of rat heart and decreased the contents of AST,LDH and MDA in serum.Compared with the blank group,11 heart biomarkers and 10 plasma biomarkers related to myocardial ischemia were screened,and Metabo Analyst pathway analysis found five metabolic pathways that may be related to myocardial ischemia.Conclusion Kudiezi Injection prevented myocardial ischemia by regulating glutathione metabolism,glycerophospholipid metabolism and linolenic acid metabolism.This study not only provided the basis for elucidating the mechanism of Kudiezi Injection in preventing myocardial ischemia,but also provided reference for the rational clinical application of Kudiezi Injection.