冠心病心血瘀阻证与气阴两虚证尿液代谢组学分析

Analysis of Urine Metabolomics Between Blood Stasis in Heart Syndrome and Qi-Yin Deficiency Syndrome in Coronary Heart Disease

目的采用代谢组学的方法和技术比较研究冠心病心血瘀阻证与气阴两虚证的生化代谢产物差异谱。方法收集符合标准的心血瘀阻证、气阴两虚证冠心病患者各50例,两组受试者上午8∶00—10∶00收集尿液标本,应用亲水相互作用超高效液相色谱与四级杆飞行时间质谱技术,比较冠心病心血瘀阻证与气阴两虚证患者尿液的差异性代谢物,结合KEGG通路,研究分析受到显著影响的代谢通路,用机器学习统计分析法探寻特征性生物标志物,从代谢组学角度研究阐明中医证候相关的多因素调节网络。结果与冠心病气阴两虚证患者相比,冠心病心血瘀阻证患者尿液的显著性差异代谢物有6种,差异代谢物有8种,与上述代谢物相关的代谢通路主要有精氨酸生物合成,缬氨酸、亮氨酸与异亮氨酸的合成,丙氨酸、天冬氨酸和谷氨酸代谢,矿物质代谢等,筛选出冠心病心血瘀阻证的特征性生物标志物2种分别是α-N-苯-L-谷氨酰胺和精氨酸-丝氨酸。结论尿液代谢生物标记物的变化能在一定程度上区分冠心病心血瘀阻证与气阴两虚证,为冠心病不同中医证型的现代阐述提供了参考。

Objective The metabolomic methods and techniques were applied to compare the difference in biochemical meta-bolic products between blood stasis in heart syndrome and Qi-Yin deficiency syndrome in coronary heart disease(CHD).Meth-ods The urine of 100 CHD patients were collected from 8 to 10 o'clock in the morning,including 50 patients with blood stasis in heart syndrome and 50 patients with Qi-Yin deficiency syndrome.Hydrophilic interaction ultra-high performance liquid chro-matography and quadrupole time-of-flight mass spectrometryapplied were applied to compare the difference of urine metabolo-mics between blood stasis in heart syndrome and Qi-Yin deficiency syndrome in CHD.Then the significantly affected metabolic pathways were explored with the KEGG.And the machine learning statistical analysis was used to explore the characteristic bio-markers.The multi-factor regulatory network of TCM syndromes were expounded from the perspective of metabolomics.Results Compared with CHD patients with Qi-Yin deficiency syndrome,there were 6 significantly different metabolites and 8 differential metabolites in the urine of CHD patients with blood stasis in heart syndrome.The metabolic pathways related to the above metab-olites mainly included arginine biosynthesis,synthesis of valine,leucine and isoleucine,metabolism of alanine,aspartate and gluta-mate,mineral metabolism,etc.Two characteristic biomarkers of CHD with blood stasis in heart syndrome wereα-N-benzene-l-glutamine and arginine serine.Conclusion The difference of urine metabolic biomarkers can distinguish patients with blood stasis in heart syndrome and Qi-Yin deficiency syndrome in CHD,which is a scientific basis to clarify the concept of TCM syn-drome in CHD.