急性ST段抬高型心肌梗死患者的血清代谢组学研究

Serum metabolomics in patients suffered from acute ST segment elevation myocardial infarction

目的:分析急性ST段抬高型心肌梗死(acute ST-segment elevation myocardial infarction,ASTEMI)患者的血清,找出特异性的代谢产物。方法:运用超高效液相色谱与四级杆飞行时间串联质谱仪联用技术(ultraperformance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry,UPLC-Q-TOF-MS/MS)和多维统计分析结合单维统计分析的方法,比较ASTEMI患者组(n=15)和健康对照组(n=10)的血清。同时采用化学发光法检测ASTEMI患者组(n=15)和健康对照组(n=10)血清中的硫酸脱氢表雄酮(dehydroepiandrosterone sulfate,DHEAS)含量,进一步证实ASTEMI患者的部分代谢组学研究结果。结果:经UPLC-Q-TOF-MS/MS分析后发现ASTEMI患者组和健康对照组具有不同的代谢特征。在多维统计分析中,主成分分析(principal component analysis,PCA)和偏最小二乘判别分析(partial least squares discriminant analysis,PLS-DA)结果显示ASTEMI患者组和健康对照组分布在不同区域。结合多维统计分析和单维统计分析方法,发现ASTEMI患者组血清中至少有9个代谢产物明显不同于健康对照组。经过代谢组学研究发现的部分差异(ASTEMI患者组血清中的DHEAS含量明显低于健康对照组),进一步采用化学发光法检测证实(P=0.000)。结论:通过代谢组学分析发现ASTEMI患者血清代谢水平明显不同于健康对照者。在ASTEMI患者血清中至少有9个代谢产物与该疾病相关。这些发现可能提供关于ASTEMI患者代谢改变的新见解。

Objective:To identify the specific metabolic changes by performing the metabolomics analyses on the serum of patients suf fered from acute ST-segment elevation myocardial infarction(ASTEMI). Methods:Ultraperformance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) and multivariate statistical analysis combined with statistical analysis unit were used to analyze the serum of ASTEMI patients group(n=15)in comparison with the healthy control group(n=10). Further chemiluminescence detection of dehydroepiandrosterone sulfate(DHEAS)was carried out to verify some of the metabolomics findings from the ASTEMI patients. Results:UPLC-Q-TOF-MS/MS revealed that ASTEMI patients and healthy control individuals exhibited distinct metabolomics profiles. Principal component analysis(PCA)and partial least squares discriminant analysis(PLS-DA)demonstrated that ASTEMI patients and healthy control groups were resided in different regions. By using multivariate statistical analysis and statistical analysis,at least nine metabolites were found to markedly differ in the serum of ASTEMI group from those in the healthy individuals. Some differences revealed by the metabolomics study,such as the significant reduction of DHEAS in the serum of ASTEMI patients,were further confirmed by independent chemiluminescence measure ments(P=0.000). Conclusion:The unbiased metabolomics analyses reveal that there are significant differences between ASTEMI patients and healthy controls at serum metabolite levels. At last nine metabolites in the serum are found to be associated with ASTEMI. These findings may provide new insights regarding the metabolism alterations in ASTEMI patients.