活血益心方干预急性冠脉综合征气虚血瘀证的代谢组学研究
Metabonomics Study of Huoxue Yixin Formula for the Treatment of Qi Deficiency and Blood Stasis Syndrome of Acute Coronary Syndrome
冯娟 1朱翠玲 2段飞 2孙彦琴 2谢梦欣 1刘晓萌 1刘刚 2闫奎坡2
作者信息
- 1. 河南中医药大学(郑州 450000)
- 2. 河南中医药大学第一附属医院(郑州 450000)
- 折叠
摘要
目的:探讨活血益心方治疗急性冠脉综合征气虚血瘀证的作用机制.方法:13 例急性冠脉综合征病人按随机数字表分为治疗组和对照组,利用高效液相色谱-质谱联用技术检测两组病人治疗前后的血清代谢物,并将两组病人与非冠心病人群的代谢谱进行对比分析,筛选出差异代谢物,预测与疾病治疗相关的代谢通路.结果:急性冠脉综合征人群具有特异的代谢谱,与非冠心病人群代谢谱存在显著差异.与对照组相比,活血益心方干预后,急性冠脉综合征人群血清熊去氧胆酸、鞘氨醇、甲基丙二酸等 9种物质表达水平明显上调,去甲肾上腺素、丙酮酸、L-色氨酸等 21种物质表达水平明显下调.差异代谢物通路分析发现,活血益心方治疗急性冠脉综合征的作用机制主要涉及 2型糖尿病、低氧诱导因子(HIF)-1信号通路、环磷酸腺苷(cAMP)信号通路、烟酸和烟酰胺代谢、胆固醇代谢、泛酸和辅酶 A生物合成、三羧酸循环、心肌细胞的肾上腺素能信号传导、氧化磷酸化.结论:鉴定出 30 个潜在生物标志物,涉及 2型糖尿病、HIF-1信号通路、cAMP信号通路等 15条代谢途径,主要参与心肌细胞的氧化应激、心肌细胞的兴奋-收缩偶联、动脉粥样硬化炎症反应、细胞凋亡和乙酰化反应等生物学过程.本研究利用代谢组学技术揭示了疾病和中药复方干预后机体到底发生了什么,从代谢终端产物层面阐述了活血益心方治疗急性冠脉综合征的作用机制,为后续试验的开展和新药的研发提供一定的参考依据.
Abstract
Objective:To explore the mechanism of Huoxue Yixin Formula for the treatment of Qi deficiency and blood stasis syndrome of acute coronary syndrome.Methods:According to the random digital table,13 patients with acute coronary syndrome were randomly divided into treatment group and control group.The serum metabolites of two groups before and after treatment were detected by high performance liquid chromatography-mass spectrometry.The metabolic profiles of two groups were compared with patients without coronary heart disease to screen out the potential metabolites,and metabolic pathways associated with disease treatment were then predicted.Results:Patients with acute coronary syndrome had some specific metabolic spectrum,which was significantly different from patients without coronary heart disease.Compared with the control group,the expression levels of 9 substances such as ursodeoxycholic acid,sphinganine,methylmalonic acid significantly up-regulated,and the expression levels of 21 substances such as norepinephrine,pyruvic acid,L-tryptophan significantly down-regulated after the intervention of Huoxue Yixin Formula.Differential metabolite pathway analysis showed that the mechanism of Huoxue Yixin Formula for the treatment of acute coronary syndrome mainly related to typeⅡ diabetes mellitus,hypoxia inducible factor 1(HIF-1)signaling pathway,cyclic adenosine monophosphate(cAMP)signaling pathway,nicotinate and nicotinamide metabolism,cholesterol metabolism,pantothenate and coenzyme A(CoA)biosynthesis,citrate cycle,adrenergic signaling in cardiomyocytes,oxidative phosphorylation.Conclusion:Thirty potential biomarkers were identified,involving 15 metabolic pathways.This study revealed what happened in the body after the intervention of the disease and traditional Chinese medicine by metabolomics technology,and elaborated the mechanism of Huoxue Yixin Formula for the treatment of acute coronary syndrome from the level of metabolic end products.It provided a certain reference for the follow-up trials,the research and development of new drugs.
关键词
急性冠脉综合征/活血益心方/代谢组学/高效液相色谱-质谱联用技术Key words
acute coronary syndrome/Huoxue Yixin Formula/metabonomics/high performance liquid chromatography-mass spectrometry引用本文复制引用
基金项目
国家自然科学基金青年基金(81303073)
河南省科技攻关计划(192102310161)
河南省科技攻关计划(182102310291)
河南省自然科学基金青年基金(232300421308)
河南省中医药科学研究专项(2021ZY1015)
河南省中医药科学研究专项(2021ZY2004)
河南省中医药科学研究专项(2021ZY2006)
河南省卫生健康委基地专项(2021JDZY081)
河南省卫生健康委基地专项(2021JDZY038)
出版年
2024