基于代谢组学分析急性心肌梗死大鼠尿液代谢物变化

Urine Metabolites Changes in Acute Myocardial Infarction Rats via Metabolomic Analysis

目的通过非靶向代谢组学研究急性心肌梗死(acute myocardial infarction,AMI)大鼠尿液代谢产物的变化,筛选出可用于AMI法医学鉴定的生物标志物。方法建立假手术组、AMI组和高脂血症+AMI组(hyperlipidemia+acute myocardial infarction,HAMI)大鼠模型。运用超高效液相色谱-质谱法(ultra-high performance liquid chromatography-mass spectrometry,UPLC-MS)分析AMI大鼠尿液代谢谱的变化。通过主成分分析、偏最小二乘判别分析、正交偏最小二乘判别分析等筛选差异代谢物。使用MetaboAnalyst数据库进行代谢通路富集分析并评估差异代谢物的预测能力。结果分别筛选出40种和61种与AMI相关和HAMI相关的差异代谢物。其中22种为共同代谢物,这些小分子代谢物主要集中在烟酸和烟酰胺代谢途径中。在95%可信区间内N8-乙酰亚精胺、3-甲基组胺和胸腺嘧啶的受试者操作特征曲线的曲线下面积(area under the curve,AUC)值大于0.95。结论N8-乙酰亚精胺、3-甲基组胺和胸腺嘧啶可作为诊断AMI的潜在生物标志物,烟酸和烟酰胺代谢的异常可能是AMI的主要原因。本研究可为AMI的作用机制和死因鉴定提供参考。

Objective To screen biomarkers for forensic identification of acute myocardial infarction(AMI)by non-targeted metabolomic studies on changes of urine metabolites in rats with AMI.Methods The rat models of the sham surgery group,AMI group and hyperlipidemia+acute myocardial infarction(HAMI)group were established.Ultra-high performance liquid chromatography-mass spectrometry(UPLC-MS)was used to analyze the changes of urine metabolic spectrometry in AMI rats.Principal component analysis,partial least squares-discriminant analysis,and orthogonal partial least squares-discriminant analysis were used to screen differential metabolites.The MetaboAnalyst database was used to analyze the metabolic pathway enrichment and access the predictive ability of differential metabolites.Results A total of 40 and 61 differential metabolites associated with AMI and HAMI were screened,respectively.Among them,22 metabolites were common in both rat models.These small metabolites were mainly concentrated in the niacin and nicotinamide metabolic pathways.Within the 95%confidence interval,the area under the curve(AUC)values of receiver operator characteristic curve for N8-acetylspermidine,3-methylhistamine,and thymine were greater than 0.95.Conclusion N8-acetylspermidine,3-methylhistamine,and thymine can be used as potential biomarkers for AMI diagnosis,and abnormal metabolism in niacin and nicotinamide may be the main causes of AMI.This study can provide reference for the mechanism and causes of AMI identification.