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代谢组学分析急性心肌梗死大鼠尿液代谢产物的变化。

Urine Metabolites Changes in Acute Myocardial Infarction Rats via Metabolomic Analysis.

机构信息

School of Forensic Medicine, Shanxi Medical University, Jinzhong 030600, Shanxi Province, China.

Yinzhou District Public Security Judicial Appraisal Center, Ningbo 315100, Zhejiang Province, China.

出版信息

Fa Yi Xue Za Zhi. 2024 Jun 25;40(3):227-236. doi: 10.12116/j.issn.1004-5619.2023.431108.

Abstract

OBJECTIVES

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.

CONCLUSIONS

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.

摘要

目的

通过对急性心肌梗死(AMI)大鼠尿液代谢物变化的非靶向代谢组学研究,筛选用于法医鉴定的生物标志物。

方法

建立假手术组、AMI 组和高脂血症+急性心肌梗死(HAMI)组大鼠模型。采用超高效液相色谱-质谱联用(UPLC-MS)分析 AMI 大鼠尿液代谢谱的变化。采用主成分分析、偏最小二乘判别分析和正交偏最小二乘判别分析筛选差异代谢物。使用 MetaboAnalyst 数据库对代谢通路进行富集分析,并评估差异代谢物的预测能力。

结果

分别筛选出与 AMI 和 HAMI 相关的 40 种和 61 种差异代谢物。其中,22 种代谢物在两种大鼠模型中均存在。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%置信区间内,N8-乙酰亚精胺、3-甲基组氨酸和胸腺嘧啶的受试者工作特征曲线下面积(AUC)值均大于 0.95。

结论

N8-乙酰亚精胺、3-甲基组氨酸和胸腺嘧啶可作为 AMI 诊断的潜在生物标志物,烟酸和烟酰胺的异常代谢可能是 AMI 的主要原因。本研究可为 AMI 鉴定的机制和病因提供参考。

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