摘要
目的:采用代谢组学技术和方法对冠心病(coronary heart disease,CHD)心血瘀阻证与气阴两虚证患者的唾液样本进行非靶向代谢组学分析,比较唾液样本的代谢产物差异谱。方法:收集CHD心血瘀阻证和气阴两虚证患者各50例,采用亲水相互作用超高效液相色谱与四级杆飞行时间质谱(hydrophilic interaction chromatography ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry,HILIC UHPLC-Q-TOF MS)技术,通过非靶向代谢组学分析软件XCMS对数据进行峰提取和代谢物鉴定,然后对数据进行正交偏最小二乘判别分析(orthogonal partial least squares-discriminant analysis,OPLS-DA)等多维统计分析以及t检验单维统计分析,对筛选出的显著性差异代谢物进行聚类分析和相关性分析,并综合比较影响CHD心血瘀阻证与气阴两虚证患者唾液的差异性代谢物相关代谢通路,用机器学习统计分析法探寻特征性生物标志物。结果:与CHD气阴两虚证患者相比,CHD心血瘀阻证患者唾液的差异代谢物有13种,其中显著性差异代谢物有7种(如肌酸酐、二甲基甲酰胺等),与上述代谢物相关的代谢通路主要包括蛋白质代谢,缬氨酸、亮氨酸与异亮氨酸的合成,矿物质吸收,三磷酸腺苷结合盒转运体转运蛋白等通路,筛选出CHD心血瘀阻证的4个特征性生物标志物分别是烟酰胺、β-高脯氨酸、二甲基酰胺和肌酸酐。结论:唾液代谢生物标记物的变化能在一定程度上区分CHD心血瘀阻证与气阴两虚证的生化代谢物组谱特征。
Objective:To investigate potential differences in salivary metabolite profiles by conducting an untargeted metabolomics analysis comparing patients with heart blood stasis and obstruction syndrome to those with Qi-Yin deficiency syndrome.Methods:Having enrolled 50 patients each with CHD of heart blood stasis and obstruction syndrome and Qi-Yin deficiency syndrome,HILIC UHPLC-Q-TOF MS technology was adopted to conduct the peak extraction and metabolite identification of the data via untargeted metabolomics analysis software,subsequently,to perform multidimensional statistical analyses,including OPLS-DA,as well as t-test(univariate analysis)of the data,and to conduct cluster analysis and correlation analysis on the filtered significant differential metabolites,and to generally compare the relevant metabolic pathways involving differential metabolites in saliva between patients with heart blood stasis and obstruction syndrome,and these with Qi-Yin deficiency syndrome,characteristic biomarkers were identified using machine learning and statistical analysis.Results:Compared with the patients with Qi-Yin deficiency syndrome,there were 13 differential metabolites in saliva of patients with heart blood stasis and obstruction syndrome,among them,seven differentially expressed metabolites were identified,including creatinine(Cr),N,N-dimethylformamide(DMF)and others,metabolic pathways associated with the above-mentioned metabolites primarily covered protein metabolism,biosynthesis of valine,leucine and isoleucine,mineral absorption,ATP-binding cassette(ABC)transporters,and four characteristic biomarkers for CHD with heart blood stasis and obstruction syndrome were nicotinamide,β-Homoproline,DMF and Cr respectively.Conclusion:The alterations in salivary metabolic biomarkers can differentiate the biochemical metabolomic profiles between CHD patients with heart blood stasis and obstruction syndrome and those with Qi-Yin deficiency syndrome to a certain extent.
作者
王恒和
张冠
WANG Henghe;ZHANG Guan(First Teaching Hospital of Tianjin University of TCM/National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion,Tianjin 300193,China;Graduate School of Tianjin University of Traditional Chinese Medicine,Tianjin 300193,China)
出处
《西部中医药》
2026年第2期122-130,共9页
Western Journal of Traditional Chinese Medicine
基金
国家自然科学基金面上项目(81573849)。
关键词
冠心病
中医证候
心血瘀阻证
气阴两虚证
代谢组学
唾液
证候基础
coronary heart disease
TCM syndrome
heart blood stasis and obstruction syndrome
Qi-Yin deficiency syndrome
metabolomics
saliva
syndrome basis
