急性脑梗死的血浆代谢标志物研究

Plasma metabolomics biomarkers study on acute ischemic stroke

目的通过血浆代谢组学研究筛选急性脑梗死患者的特异性生物标志物。方法采用气相色谱-质谱法检测急性脑梗死患者(S)、疾病对照患者(DC)和健康对照者(HC)的血浆代谢组。利用正交偏最小二乘法明确任意两组间的代谢物差异,并以受试者工作特征(ROC)曲线评价含量异常的代谢物对于脑梗死的诊断价值。结果 S与DC组、S与HC组、DC与HC组间分别有26、16、23种含量不同的代谢物。其中,12种代谢物在S组与DC组和S组与HC组间均差异显著。ROC曲线检测显示这12种代谢物中的丁酸、2-哌啶甲酸、焦谷氨酸和棕榈酸对于脑梗死的诊断均有较高敏感性或特异性。结论代谢组学研究是探寻脑梗死生物学标志物的有力工具。丁酸、焦谷氨酸、2-哌啶甲酸和棕榈酸可能成为脑梗死的潜在诊断生物学标志物。

Objective To screen the specific biomarkers for acute cerebral infarction by plasma metabolism study.Methods Gas chromatography/mass spectrometry technique was employed to investigate the plasma metabolic differences between individuals that had acute ischemic stroke(S),other diseases controls(DC),or healthy controls(HC).The difference in metabolism between any two groups was revealed by orthogonal partial least squares discriminant analysis.Receiver-operator characteristic(ROC)curve was used to verify the diagnostic potential of the dysregulated metabolites after ischemic stroke.Results Twenty-six,16,and 23 metabolites showed statistically significant differences between S and HC,S and DC,and DC and HC groups,respectively.Among them,the plasma level of 12 metabolites had consistent changes both between S and HC group,and between S and DC group.ROC curve showed that butanoic acid,pyroglutamic acid,2-piperidinecarboxylic acid and hexadecanoic acid in the 12 metabloites had high sensitivity or specificity for ischemic stroke.Conclusion Metabolomic approach is a powerful tool to search for biomarkers of ischemic stroke.Butanoic acid,pyroglutamic acid,2-piperidinecarboxylic acid and hexadecanoic acid are potential biomarkers for ischemic stroke.