基于靶向代谢组学分析糖尿病肾脏疾病血清中苯丙氨酸代谢途径代谢物的变化

Analysis on the changes of serum phenylalanine metabolites in diabetic renal disease based on targeted metabolomics

目的:应用靶向代谢组学方法研究糖尿病肾脏疾病(diabetic kidney disease,DKD)患者与健康对照者血清中苯丙氨酸代谢途径的代谢物的变化,综合分析血清差异代谢物变化规律及其与临床指标的相关性。方法:选取包头医学院第一附属医院肾内科住院部20例DKD患者作为疾病研究组,20例健康体检者作为正常对照组(NC),收集血液标本。经液相色谱/质谱(LC/MS)检测,采用靶向代谢组学分析苯丙氨酸代谢途径中的血清代谢物的差异性,进行单变量及多变量分析和统计学分析,阐明血清代谢物在DKD中的意义。结果:与健康对照组相比,DKD患者血清中苯丙氨酸途径的代谢产物苯丙氨酸(L-Phenylalanine)、马尿酸(Hippuric-acid)、D-苯乙酰基-L-谷氨酰胺(Phenlacetyl-L-Glutamine)的含量高于对照组(P<0.05)。对血清代谢物参与的通路富集分析显示,苯丙氨酸代谢通路参与DKD的发展过程。DKD患者苯丙氨酸途径的血清代谢产物苯丙氨酸、马尿酸、D-苯乙酰基-L-谷氨酰胺与临床指标Scr、FBG、HbA1c呈正相关。结论:苯丙氨酸代谢途径可能参与DKD的发生发展。

Objective:To study the changes of phenylalanine metabolites in serum of diabetic kidney disease(DKD)patients and healthy controls using targeted metabolomics,and to comprehensively analyze the change rule of differential metabolites in serum and its correlation with clinical indicators.Methods:The inpatients in the Department of Nephrology of the First Affiliated Hospital of Baotou Medical College were selected as the research subjects.20 DKD patients were selected as the study group and 20 healthy subjects as the control group.Blood samples were collected from the two groups.The difference of serum metabolites was analyzed by liquid chromatography/mass spectrometry(LC/MS)and targeted metabolomics.Univariate and multivariate analysis and statistical analysis were performed to analyze the difference of serum metabolites and clarify their significance in DKD.Results:Serum levels of Phenylalanine metabolites(L-phenylalanine,Hippuric acid,D-phenlacetyl-L-glutamine)in DKD patients were significantly higher than those in control group.The enrichment analysis of the pathway involved in serum metabolites showed that phenylalanine metabolism pathway was involved in the progress of DKD.Serum metabolites of phenylalanine metabolism pathway in DKD patients,including L-phenylalanine,Hippuric acid and D-phenlacetyl-L-glutamine,were positively correlated with Scr,FBG and HbA1c.Conclusion:Phenylalanine metabolism pathway may be involved in the occurrence and development of DKD.