真武汤对心肌梗死后心力衰竭大鼠血清代谢组的作用研究  

Study on the Effect of Zhenwu Decoction(真武汤)on Serum Metabolomics in Heart Failure Rats after Myocardial Infarction

作　　者：毛飞 徐闵 丁欣 谭光国 周倩 MAO Fei;XU Min;DING Xin;TAN Guangguo;ZHOU Qian(Beijing Children's Hospital of Capital Medical University,Beijing 100045,China;General Hospital of Central Theater Command,Wuhan 430070,Hubei,China;Air Force Medical University,Xi’an 710032,Shaanxi,China;The First Affiliated Hospital of Air Force Medical University,Xi’an 710032,Shaanxi,China)

机构地区：[1]首都医科大学附属北京儿童医院,北京100045 [2]中国人民解放军中部战区总医院,湖北武汉430070 [3]空军军医大学,陕西西安710032 [4]空军军医大学第一附属医院,陕西西安710032

出　　处：《辽宁中医药大学学报》2025年第4期11-16,共6页Journal of Liaoning University of Traditional Chinese Medicine

基　　金：国家自然科学基金(82003916);陕西省重点产业链资助项目(2022ZDLSF05-06)。

摘　　要：目的研究真武汤对心肌梗死后心力衰竭大鼠血清代谢物组的影响。方法以冠状动脉左前降支结扎制备心肌梗死后心力衰竭大鼠模型,以左前降支处穿线不结扎制备假手术组,造模后给予真武汤治疗4周,测定血清乳酸脱氢酶1(LDH1)、肌酸激酶(CK)和肌酸激酶同工酶(CK-MB),超声心动图测定左心室射血分数(EF)和缩短分数(FS),超高效液相色谱-四极杆飞行时间质谱(UHPLC-Q-TOFMS)结合多变量统计分析进行血清代谢组学分析。结果模型组血清LDH1、CK、CK-MB水平明显升高,EF、FS值明显下降,经真武汤治疗后上述指标显著改善。血清代谢物在三维主成分分析(3D-PCA)得分图中得到明显区分,结合正交偏最小二乘法判别分析的S-plot载荷图和单因素统计分析,鉴定了17种心肌梗死后心力衰竭相关血清生物标志物,真武汤对其中的13种具有显著的回调作用,代谢通路分析显示真武汤主要的靶向代谢通路为花生四烯酸代谢、色氨酸代谢、丙酮酸代谢、三羧酸循环、鞘脂代谢、支链氨基酸代谢、甘油磷脂代谢、脂肪酸代谢。结论真武汤能通过调节失衡的花生四烯酸代谢、色氨酸代谢、丙酮酸代谢、三羧酸循环、鞘脂代谢、支链氨基酸代谢、甘油磷脂代谢、脂肪酸代谢发挥抗心力衰竭的作用。Objective To explore effects of Zhenwu Decoction(真武汤,ZWD)on the serum metabolome in heart failure rats after myocardial infarction.Methods The rat model of myocardial infarction-induced heart failure was established by permanent ligature of the left anterior descending(LAD).ZWD-treated rats were dosed for 4 weeks after molding.The serum lactate dehydrogenase1(LDH1),creatine phosphatase isoenzyme(CK),creatine phosphatase isoenzyme MB(CK-MB)were measured.The ejection fraction(EF)and shortening fraction(FS)were measured by echocardiography.The combination of ultrahigh-performance liquid chromatography(UHPLC)-high resolution MS with multivariate statistical analysis was used to detect the differences of metabolites in serum.Results The levels of serum LDH1,CK and CK-MB were significantly increased in the model group,and the values of EF and FS decreased significantly.However,the indicators were significantly improved after treatment with ZWD.Threedimentional principal component analysis(3D-PCA)score plot demonstrated that the serum metabolic profiling could be obviously distinguished between sham group and model group or between ZWD-treated and model groups.17 serum biomarkers were identified based on the combination of the S-plot generated from OPLS-DA and univariate statistical analysis.ZWD had significant reversal effect on 13 metabolites.Metabolic pathway analysis showed that arachidonic acid metabolism,tryptophan metabolism,pyruvate metabolism,tricarboxylic acid cycle,sphingolipid metabolism,branched chain amino acids,glycerophospholipid metabolism,and fatty acid metabolism were the main targeted metabolic pathways of ZWD.Conclusion ZWD can improve heart failure by regulating the unbalanced metabolic pathways,including arachidonic acid metabolism,tryptophan metabolism,pyruvate metabolism,tricarboxylic acid cycle,sphingolipid metabolism,branched chain amino acids,glycerophospholipid metabolism,and fatty acid metabolism.

关 键 词：心力衰竭 代谢组学 液质联用 真武汤 作用机制 

分 类 号：R285.5[医药卫生—中药学]