Abstract: Objective　To investigate the mechanisms of lipid metabolic disorders and identify differential lipid metabolites in a rat model of isoproterenol (ISO)-induced myocardial ischemia (MI).Methods　A rat model of MI was established by intraperitoneal injection of a high dose of isoproterenol for two consecutive days. Cardiac function was assessed using echocardiography. The serum markers of myocardial injury were measured. Lipid metabolites in rat myocardial tissue were profiled using liquid chromatography-mass spectrometry (LC-MS). Multivariate statistical analyses, including Principal Component Analysis (PCA) and Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA), were employed to screen for differential lipids.Results　Compared with the control group, the model group exhibited a significant decrease in stroke volume (SV) and cardiac output (CO) (P<0.01), along with a significant increase in left ventricular anterior wall systolic thickness (LVAWs), left ventricular anterior wall diastolic thickness (LVAWd), left ventricular posterior wall systolic thickness (LVPWs), and left ventricular posterior wall diastolic thickness (LVPWd) (P<0.01). Serum levels of LDH, CK-MB, and cTnT were significantly elevated (P<0.01). Lipidomics analysis revealed distinct myocardial lipid metabolic profiles between the two groups, leading to the identification of 92 differential lipid metabolites. Compared to the control group, the model group showed significantly decreased levels of long-chain acylcarnitines and phosphatidylcholines, while the contents of oxidized phosphatidylcholines, triglycerides, oxidized triglycerides, and ceramides were significantly increased. Conclusion　Lipidomics technology effectively characterized myocardial energy metabolism dysfunction and lipid peroxidation in the ISO-induced myocardial ischemia model, providing insights into its underlying pathological mechanisms.

Key words: liquid chromatography-mass spectrometry (LC-MS), lipidomics, myocardial ischemia, biomarkers, isoproterenol

摘要： 目的　基于脂质组学技术探讨异丙肾上腺素(ISO)致心肌缺血(MI)大鼠模型的脂质代谢紊乱机制及其差异 脂质代谢物。方法　采用连续两天腹腔注射高剂量ISO构建MI大鼠模型,以超声心动图评价心功能;检测血清心 肌损伤标志物;应用液相色谱-质谱联用(LC-MS)检测大鼠心肌组织脂质代谢物,结合主成分分析、正交偏最小二 乘-判别分析筛选差异脂质。结果　与对照组相比,模型组大鼠心博量(SV)、心输出量(CO)显著降低(P<0.01), 左心室前壁收缩期厚度(LVAWs)、左心室前壁舒张期厚度(LVAWd)、左心室后壁收缩期厚度(LVPWs)、左心室后 壁舒张期厚度(LVPWd)显著升高(P<0.01);血清LDH、CK-MB以及cTnT含量显著升高(P<0.01);脂质组学分析 显示,两组大鼠的心肌脂质代谢谱存在明显差异,共检测出92种差异脂质代谢物。与对照组相比,模型组中长链 酰基肉碱、磷脂酰胆碱等含量显著下降,氧化磷脂酰胆碱、甘油三酯、氧化甘油三酯及神经酰胺等含量显著上升。 结论　脂质组学技术可有效表征ISO致MI模型的心肌能量代谢障碍与脂质过氧化反应,为揭示其发病机制提供 依据。

关键词: 液质联用, 脂质组学, 心肌缺血, 生物标志物, 异丙肾上腺素