老年急性心肌梗死患者儿茶酚代谢特征分析

Analysis of metabolomic marker pyrocatechol in elderly patients with acute myocardial infarction

目的 分析老年急性心肌梗死患者的血浆代谢组学特征,探索其潜在的代谢标志物.方法 横断面研究,入选苏州大学附属第二医院急性心肌梗死老年患者30例(心肌梗死组),于体检中心筛选30例符合纳入标准的老年人为对照组,利用UHPLC-QTOF/MS技术检测其血浆中代谢物,在京都基因与基因组(KEGG)数据库中搜索整理所有代谢物的信息.通过主成分分析(PCA)和正交偏最小二乘法-判别分析(OPLS-DA)对比两组样本代谢物的总体趋势,利用Mann-Whitney U检验初步筛选差异代谢物.联合Mann-Whitney U检验、互信息和随机森林模型进一步分析差异代谢物的重要性,运用靶向代谢组学检测重要差异代谢物在两组样本中的含量,对两组数据进行 t检验比较其差异.结果 心肌梗死组和对照组患者中,高血压、高脂血症及糖尿病患病率比较,差异无统计学意义(均P>0.05),心肌梗死组患者血浆肌钙蛋白T(2.16±0.36)μg/L含量高于对照组(0.26±0.03)μg/L(t=5.17,P<0.05).两组样本的总体趋势在PCA得分图和OPLS-DA模型中得到明显区分,样本中有32个差异代谢物符合初步筛选标准.进一步分析得出重要差异代谢物包括儿茶酚和4种氨基酸组成的小肽段,其与分组关系密切,且预测分组准确性的能力强.靶向代谢组学检测结果显示,儿茶酚在心肌梗死组的浓度为(310.3±40.0)ng/L,对照组为(2 607.0±758.1)ng/L,两组比较差异有统计学意义(t=5.34,P<0.01).结论 血浆儿茶酚具有成为老年急性心肌梗死患者代谢标志物的潜力,可能与该病的发生及预后密切相关.

Objective To analyze the plasma metabolomic characteristics of elderly patients with acute myocardial infarction and identify potential metabolic makers.Methods Thirty elderly patients with acute myocardial infarction at the Second Affiliated Hospital of Soochow University were enrolled into the myocardial infarction group and thirty elderly people recruited at the physical examination center and meeting the inclusion criteria served as the control group.Plasma metabolites were measured by ultra-high performance liquid chromatography and quadrupole time-of-flight mass spectrometry.Information about metabolites was searched and sorted via the Kyoto Encyclopedia of Genes and Genomes(KEGG)database.Principal component analysis and orthogonal partial least square-discriminant analysis were carried out to compare overall trends and the Mann-Whitney U test was used for preliminary screening of differential metabolites in the two groups.Then the Mann-Whitney U test and a model of mutual information with random forests were used to analyze the importance of differential metabolites.A tandem liquid chromatography-mass spectrometry-based approach was subsequently performed for targeted detection of the content of differential metabolites in the two groups,and the t-test was used for comparison between the two groups.Results There were no significant differences in the prevalence of hypertension,hyperlipidemia and diabetes mellitus between the two groups(P>0.05),while the plasma troponin T level in the myocardial infarction group was significantly higher than that in the control group,(2.16±0.36)μg/L vs.(0.26±0.03)μg/L(t=5.17,P<0.05).A clear difference in the overall trend was presented on the scatter plot of PCA and OPLS-DA,and a total of 32 differential metabolites met the preliminary screening criteria.Further analysis showed that pyrocatechol and 4 small peptides were closely correlated with grouping and was strongly predictive of group designation.Targeted quantification revealed the pyrocatechol concentration was(310.3±40.0)ng/L in the myocardial infarction group and(2607.0±758.1)ng/L in the control group.The difference between the two groups was statistically significant(P<0.01).Conclusions Plasma pyrocatechol has the potential to be metabolic marker of acute myocardial infarction in elderly patients and might be closely related to the occurrence and prognosis of this disease.