摘要
目的应用代谢组学技术研究冠心病(coronary heart disease,CHD)患者血浆中小分子代谢物的变化,筛选出可用于CHD早期临床诊断和法医学鉴定的生物标志物。方法收集冠心病患者及健康人群血浆样本各20例,应用超高效液相色谱-四极杆-飞行时间质谱联用技术(UPLC-QTOF/MS)检测样本代谢物谱;SIMCA-P 14.1软件通过主成分分析(principal component analysis,PCA)、偏最小二乘法-判别分析(partial least squares methoddiscriminant analysis,PLS-DA)及正交偏最小二乘法-判别分析(orthogonal PLS-DA,OPLS-DA)进行数据模式识别,根据模型中的变量权重重要性排序值(variable importance in projection, VIP)结合Mann-Whitney U检验,寻找CHD患者血浆中的差异代谢物。结果 CHD患者与健康人群血浆样本在代谢物水平存在明显差异,与健康人群相比,CHD患者血浆中共筛选出26个高度相关的差异代谢物,其中13个水平下调,13个水平上调,依据血浆代谢谱建立的PLS-DA、OPLS-DA模型可对CHD患者与健康人群进行有效判别。结论 CHD患者血浆中的差异代谢物有望成为预防、诊断及法医学鉴定CHD的潜在生物标志物,可为CHD的诊断、临床药物治疗、预后以及法医学鉴定提供一种新的研究思路。
Objective To study the changes of small and medium molecular metabolites in plasma of CHD patients by metabolomics, and to screen out small molecular biomarkers for early clinical diagnosis and forensic identification of CHD. Methods Plasma samples were collected from 20 patients with CHD and 20 healthy controls, and their metabolites were detected by ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry(UPLC-QTOF/MS). The data were entered into SIMCA-P 14.1 software for multivariate statistical analysis. Principal component analysis(PCA), partial least squares method-discriminant analysis(PLS-DA) and orthogonal partial least squares method-discriminant analysis(OPLS-DA) were used to pattern recognition as well as finding differential metabolites in the plasma of patients with CHD. Results Their were significant differences in the levels of metabolites in plasma samples between CHD and control groups Further established PLS-DA and OPLS-DA models could effectively discriminate between the case group and the control group. Compared with the control group, a total of 26 differential metabolites were screened out from the CHD plasma, of which 13 metabolites were down-regulated and 13 metabolites were up-regulated. Conclusion Differential metabolites in plasma of CHD are expected to become potential biomarkers of CHD. The study of metabolic pathways can provide a new research idea for exploring the mechanism, prognosis, clinical drug treatment as well as forensic identification about related death cause of CHD.
作者
张艺博
安国帅
谷祯
牛佳佳
杜秋香
曹洁
王英元
孙俊红
Zhang Yibo;An Guoshuai;Gu Zhen;Niu Jiajia;Du Qiuxiang;Cao Jie;Wang Yingyuan;Sun Junhong(School of Forensic Medicine,Shanxi Medical University,Taiyuan 030001,China)
出处
《中国法医学杂志》
CSCD
2020年第6期603-607,共5页
Chinese Journal of Forensic Medicine
基金
国家重点研发计划资助项目(2017YFC0803502)
山西省应用基础研究项目青年科技基金(201801D221264)。
