基于血清代谢组学分析冠心病痰瘀互结证患者的代谢差异物及通路

Analysis of metabolic differentiators and pathways in patients with coronary artery disease with phlegm and blood stasis syndrome based on serum metabolomics

关键词:  代谢组学  冠心病  痰瘀互结  中医

Key words:  metabolomics  coronary heart disease  phlegm and blood stasis  Chinese medicine

摘要:

[目的] 应用代谢组学技术分析冠心病痰瘀互结证患者血清中差异代谢物和通路，丰富冠心病痰瘀互结证的代谢组学研究。[方法] 收集天津市胸科医院2023年3—7月的冠心病患者共62例，根据疾病和证型分为冠心病痰瘀互结证组（CHD-TYHJ组）42例和正常对照组20例。空腹抽取受试者静脉血2 mL，常温静置1 h后进行血清提取，使用全自动生化仪检测两组血清中总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白胆固醇（HDL-C）和低密度脂蛋白胆固醇（LDL-C）水平，随后分析比较两组血清代谢物，并利用Metabo Analyst平台对CHD-TYHJ组的差异代谢物进行信号通路富集分析。[结果] 与CHD-TYHJ组相比，正常对照组血清HDL-C和LDL-C水平降低（P < 0.05），TC和TG水平差异无统计学意义（P > 0.05）。CHD-TYHJ组与正常对照组代谢谱区分度良好，正交偏最小二乘判别分析（OPLS-DA）模型未过度拟合，所示结果可靠。CHD-TYHJ组与正常对照组相比，在正离子模式中，共有82个代谢物上调，19个代谢物下调；在负离子模式中，共有12个代谢物上调，19个代谢物下调。与代谢物差异相关性最高的4个关键通路依次为甘油磷脂代谢、花生四烯酸代谢、亚油酸代谢和α-亚麻酸代谢。[结论] CHD-TYHJ组和正常对照组之间存在差异代谢物，其中α-亚麻酸代谢途径为首次在冠心病痰瘀互结患者血清代谢组学中发现。

Abstract:

[Objective]To apply metabolomics technology to analyze the metabolic differentiations and pathways in the serum of patients with coronary heart disease with phlegm and blood stasis syndrome, and to enrich the metabolomics study of coronary heart disease with phlegm and blood stasis syndrome.[Methods]A total of 62 patients with coronary heart disease in Tianjin Chest Hospital from March 2023 to July 2023 were collected and divided into 42 cases in the CHD-TYHJ group and 20 cases in the control group according to the disease and evidence type. The 2 mL of venous blood was drawn from the subjects on an empty stomach, and the serum was extracted after standing at room temperature for 1 hour. The levels of TC, TG, HDL-C and LDL-C in the sera of the two groups were detected by using fully automated biochemistry, followed by comparison of the metabolites in the sera of the two groups and signaling pathway enrichment analysis of the differential metabolites in the evidence of CHO-HYHJ by using the Metabo Analyst platform.[Results]Compared with the CHD-TYHJ group, serum HDL-C and LDL-C levels were reduced in the control group(P < 0.05), and there was no significant difference in TC and TG levels(P > 0.05).The metabolic profiles of the CHD-TYHJ group were well differentiated from those of the control group, and the OPLS-DA model was not overfitted, and the results shown were reliable. The metabolic profiles of the CHD-TYHJ group were better differentiated from those of the control group. Control group, a total of 82 metabolites were up-regulated and 19 metabolites were down-regulated in the positive ion model, and a total of 12 metabolites were up-regulated and 19 metabolites were down-regulated in the negative ion model. The four key pathways with the highest correlation with metabolite differences were, in order, glycerophospholipid metabolism, arachidonic acid metabolism, linoleic acid metabolism, and alpha-linolenic acid metabolism, linoleic acid metabolism, and alpha-linolenic acid metabolism.[Conclusion]Differential metabolites existed between CHD-TYHJ and control group, and the alpha-linolenic acid metabolic pathway was the first time to be found in the serum metabolomics of patients with coronary heart disease with phlegm and blood stasis syndrome.