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心通口服液治疗急性心肌梗死的代谢组学研究
引用本文:陶舒悦,梁万徽,汪 杰,张云静,方 玲,彭 灿. 心通口服液治疗急性心肌梗死的代谢组学研究[J]. 安徽中医药大学学报, 2023, 42(6): 73-78
作者姓名:陶舒悦  梁万徽  汪 杰  张云静  方 玲  彭 灿
作者单位:1.安徽中医药大学药学院,安徽 合肥 230012;2.药物制剂技术与应用安徽省重点实验室,安徽 合肥 230012;3.中药复方安徽省重点实验室,安徽 合肥 230012;4.安徽医科大学第一附属医院药剂科,安徽 合肥 230012;5.安徽省中医药研究院中药资源保护与开发研究所,安徽 合肥 230012;6.省部共建安徽道地中药材品质提升协同创新中心,安徽 合肥 230012
基金项目:亳州市科技重大专项揭榜挂帅项目(BZKXJSJ-134);安徽省科技重大专项(18030801117)
摘    要:目的 应用非靶向代谢组学技术,筛选得到急性心肌梗死(acute myocardial infarction,AMI)模型大鼠与心痛口服液治疗后AMI模型大鼠的差异代谢物及代谢通路,探讨心通口服液治疗AMI的作用机制。方法 通过左冠状动脉前降支结扎手术建立AMI大鼠模型,对动物进行分组给药,评价心通口服液的治疗效果,运用超高效液相色谱—四极杆/静电场轨道阱高分辨质谱对实验动物血清进行代谢组学分析,利用软件分析以及数据库检索筛选差异代谢物以及代谢通路。结果 大鼠心脏组织病理切片显示,模型组大鼠心肌细胞排列紊乱,心通口服液可明显逆转AMI对心肌细胞的损伤;代谢组学结果显示,心通口服液可以使胆碱、甜菜碱、硬脂酸、棕榈酸等16个代谢物发生改变,通过代谢通路富集分析发现心通口服液的治疗作用可能与不饱和脂肪酸的生物合成,甘氨酸、丝氨酸和苏氨酸代谢以及花生四烯酸代谢等代谢通路有关。结论 心通口服液能够改善AMI大鼠心脏组织的病理变化,通过调控相关代谢通路及相关代谢产物的表达,达到平衡脂质代谢与氨基酸代谢的目的,达到对AMI的治疗作用。

关 键 词:急性心肌梗死;心通口服液;代谢组学;脂质代谢;氨基酸代谢

Mechanism of Action of Xintong Oral Liquid in Treatment of Acute Myocardial Infarction: A Metabolomics Study
Affiliation:1. School of Pharmacy, Anhui University of Chinese Medicine, Anhui Hefei 230012, China; 2. Anhui Province Key Laboratory of Pharmaceutical Preparation Technology and Application, Anhui Hefei 230012, China; 3. Key Laboratory of Chinese Medicinal Formula of Anhui Province, Anhui Hefei 230012, China; 4. Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Anhui Hefei 230012, China; 5. Institute of Traditional Chinese Medicine Resources Protection and Development, Anhui Academy of Chinese Medicine, Anhui Hefei 230012, China; 6. Synergetic Innovation Center of Anhui Authentic Chinese Medicine Quality Improvement, Anhui Hefei 230012, China
Abstract:Objective To investigate the mechanism of action of Xintong Oral Liquid in the treatment of acute myocardial infarction (AMI) by using non-targeted metabolomics techniques to identify the differentially expressed metabolites and metabolic pathways in AMI model rats before and after treatment. Methods Ligation of the anterior descending branch of left coronary artery was performed to establish a rat model of AMI, and then the rats were divided into groups and administered to evaluate the therapeutic effect of Xintong Oral Liquid. Ultra-performance liquid chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry was used to perform a metabolomics analysis of serum, and related software and databases were used to identify differentially expressed metabolites and metabolic pathways. Results The observation of pathological section showed that compared with the model group with disordered arrangement of cardiomyocytes, Xintong Oral Liquid significantly reversed cardiomyocyte injury caused by AMI. The metabolomics analysis showed that Xintong Oral Liquid induced changes in 16 metabolites including choline, betaine, stearic acid, and palmitic acid, and the enrichment analysis of metabolic pathways showed that the therapeutic effect of Xintong Oral Liquid might be associated with the metabolic pathways such as biosynthesis of unsaturated fatty acids, glycine/serine/threonine metabolism, and arachidonic acid metabolism. Conclusion Xintong Oral Liquid can significantly improve heart tissue and pathological conditions in AMI rats and achieve the goal of balancing lipid metabolism and amino acid metabolism by regulating related metabolic pathways and metabolites, thereby exerting a therapeutic effect on AMI.
Keywords:Acute myocardial infarction  Xintong Oral Liquid  Metabolomics  Lipid metabolism  Amino acid metabolism
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