摘要
目的:冠心病以其极高的发病率严重威胁着人类的健康,对冠心病药物治疗及作用靶点的研究仍非常迫切。本研究旨在运用核磁共振氢谱(^(1)H nuclear magnetic resonance spectroscopy,^(1)H-NMR)代谢组学技术建立冠心病血瘀证及痰浊证的指纹代谢图谱,寻找这2种证型的血浆标志性代谢物,并揭示血府逐瘀汤治疗冠心病血瘀证的机制。方法:采集符合纳入标准的69例冠心病血瘀证患者、60例冠心病痰浊证患者及40例健康对照受试者的清晨空腹血浆,基于^(1)H-NMR构建冠心病血瘀证及痰浊证的^(1)H-NMR指纹代谢图谱。使用多元统计分析方法主成分分析(principal component analysis,PCA)、正交化偏最小二乘判别分析(orthogonal partial least squares discriminant analysis,OPLS-DA)寻找冠心病血瘀证及冠心病痰浊证的标志性代谢物。随机抽取冠心病血瘀证患者30例,予血府逐瘀汤治疗30 d,对治疗前后的清晨空腹血浆进行^(1)H-NMR检测,分析冠心病血瘀证患者服药前后标志性代谢物的变化。结果:冠心病血瘀证组与对照组存在显著性差异的代谢物有以下15种:3-羟基丁酸、乳酸、丙氨酸、谷氨酸、谷氨酰胺、丙酮酸、磷脂酰胆碱、甘油磷脂酰胆碱、甘氨酸、葡萄糖、苯丙氨酸、柠檬酸、酪氨酸、甲酸盐、极低密度脂蛋白,除葡萄糖、3-羟基丁酸、极低密度脂蛋白水平升高外,其他12种代谢物水平均下降。冠心病痰浊证组与对照组存在显著性差异的代谢物有以下16种:缬氨酸、乳酸、丙氨酸、N-乙酰-β-葡萄糖苷酶、谷氨酸、谷氨酰胺、丙酮酸、肌酸、胆碱、甘氨酸、葡萄糖、苯丙氨酸、柠檬酸、组氨酸、酪氨酸、甲酸盐,除葡萄糖和胆碱2种水平升高外,其他14种代谢物水平均下降。冠心病血瘀证患者服用血府逐瘀汤治疗后胆碱、磷脂/甘油磷脂类、肌酸、脂质、柠檬酸水平升高,乳酸水平下降。结论:^(1)H-NMR结合多
Objective: Coronary heart disease(CHD) is a serious threat to human health because of its high morbidity. It is very urgent to study the pathogenesis of CHD and the effective drug target. The purpose of this paper is using the ^(1)H-nuclear magnetic resonance spectroscopy(^(1)H-NMR) metabolomics technology to establish the metabolic fingerprint and find the potential biomarker metabolites of CHD with blood-stasis syndrome and phlegm syndrome, and to reveal the metabolic mechanism of Xuefu Zhuyu Decoction for the treatment of CHD with blood stasis syndrome.Methods: The plasma samples of 69 patients with CHD blood-stasis syndrome, 60 patients with CHD phlegm syndrome, and 40 healthy volunteers were collected in this study. Based on the ^(1)H-NMR metabolomics technology, the metabolic fingerprint of CHD with bloodstasis syndrome and phlegm syndrome was established. Multivariate statistical analysis methods including principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to find the potential biomarker metabolites of CHD with blood-stasis syndrome and phlegm syndrome. Xuefu Zhuyu Decoction was used to randomly selected blood-stasis syndrome patient. The plasma samples of pre-treatment and post-treatment were collected. ^(1)H-NMR and multivariate statistical analysis were used to analyze the changes of metabolites in patients with CHD blood-stasis syndrome before and after Xuefu Zhuyu Decoction treatment.Results: A total of 15 potential biomarkers were identified in the plasma of patients with CHD blood-stasis syndrome, including 3-hydroxybutyrate(3-HB), lactate, alanine,glutamate, glutamine, pyruvate, phosphatidylcholine(PC), glycerylphosphorylcholine(GPC), glycine, glucose, phenylalanine, citrate, tyrosine, formate, very low density lipoprotein(VLDL). The levels of glucose, 3-HB, and VLDL increased, while the levels of other 12 metabolites decreased. A total of 16 potential biomarkers were identified in the plasma of patients with CHD phlegm syndrome, includin
作者
易敏
戴幸平
李秋霞
赵玉航
聂闪闪
王东生
YI Min;DAI Xingping;LI Qiuxia;ZHAO Yuhang;NIE Shanshan;WANG Dongsheng(Department of Integrated Traditional Chinese&Western Medicine,Second Xiangya Hospital,Central South University,Changsha 410011;Department of Integrated Traditional Chinese and Western Medicine,Xiangya Hospital,Central South University,Changsha 410008,China)
出处
《中南大学学报(医学版)》
CAS
CSCD
北大核心
2021年第6期591-600,共10页
Journal of Central South University :Medical Science
基金
国家自然科学基金(81800043)。
关键词
冠心病血瘀证
冠心病痰浊证
代谢组学
核磁共振氢谱
血府逐瘀汤
coronary heart disease blood-stasis syndrome
coronary heart disease phlegm syndrome
metabolomics
^(1)H-nuclear magnetic resonance spectroscopy
Xuefu Zhuyu Decoction