[关键词]
[摘要]
目的 研究速效救心丸对心肌缺血大鼠的保护作用及对血浆代谢物的影响,初步探讨其干预心肌缺血的代谢途径和可能机制。方法 采用垂体后叶素建立大鼠心肌缺血模型,通过病理组织切片和肌酸激酶(creatine kinase,CK)、丙氨酸转氨酶(alanine aminotransferase,ALT)、天冬氨酸转氨酶(aspartate aminotransferase,AST)、羟丁酸脱氢酶(hydroxybutyrate dehydrogenase,HBDH)、乳酸脱氢酶(lactate dehydrogenase,LDH)和超氧化物歧化酶(superoxide dismutase,SOD)生化指标评估速效救心丸对心肌缺血大鼠的保护作用;采用超高效液相色谱-四级杆飞行时间质谱联用(UHPLC-QTOF/MS)技术对血浆进行代谢组学研究,筛选潜在生物标志物并富集代谢通路。结果 速效救心丸可明显改善心肌缺血大鼠心脏组织病理变化;显著降低血浆CK、AST、HBDH、LDH活性(P<0.05、0.01),升高SOD活性(P<0.05、0.01)。代谢组学分析共筛选到39个潜在生物标志物,涉及丙氨酸、天冬氨酸和谷氨酸代谢、三羧酸循环、谷氨酰胺和谷氨酸代谢等7条通路。结论 速效救心丸能够有效改善模型大鼠的心肌缺血损伤,可能通过影响能量代谢及鞘脂代谢等相关通路发挥作用。
[Key word]
[Abstract]
Objective To study the effect of Suxiao Jiuxin Pills (速效救心丸, SJP) on metabolites in plasma of rats with myocardial ischemia, and preliminarily explore the metabolic pathway and possible mechanism of its intervention on myocardial ischemia. Methods Myocardial ischemia rats model was established by pituitrin and the protective effect of SJP on heart was determined by pathological tissue sections and creatine kinase (CK), alanine aminotransferase (ALT), aspartate aminotransferase (AST), hydroxybutyrate dehydrogenase (HBDH), lactate dehydrogenase (LDH) and superoxide dismutase (SOD) biochemical tests. Metabolomics studies of plasma samples was conducted by UHPLC-QTOF/MS to screen potential biomarkers and enrich metabolic pathways. Results SJP significantly improved the pathological changes of heart in rats with myocardial ischemia; Significantly decreased the activities of CK, AST, HBDH and LDH in plasma (P < 0.05, 0.01), and increased SOD activity (P < 0.05, 0.01). A total of 39 potential biomarkers were screened, mainly involving 7 metabolic pathways including alanine, aspartic acid and glutamate metabolism, tricarboxylic acid cycle, glutamine and glutamate metabolism. Conclusion SJP can effectively improve myocardial ischemia injury in model rats, and may play a role in related pathways such as energy metabolism and sphingolipid metabolism.
[中图分类号]
R285.5
[基金项目]
北京市自然科学基金资助项目(7214284)