PCI术后肾小管功能障碍患者的尿液代谢组学研究  

Study on urine metabolism of renal tubular dysfunction after percutaneous coronary intervention

作　　者：程丽颖 周园园 邵风民[3] 王锁刚[4] 张翥 CHENG Liying;ZHOU Yuanyuan;SHAO Fengmin;WANG Suogang;ZHANG Zhu(Department of Prevention and Research in Kidney Disease,First Clinical Medical College,Henan University of Traditional Chinese Medicine,Zhengzhou 450008,China;College of Pharmacy,Zhengzhou University;Nephrology Department of Henan Provincial People’s Hospital;Department of Urology and Kidney Transplantation,First Affiliated Hospital of Henan University of Traditional Chinese Medicine;Department of Nephrology,Huazhong Fuwai Hospital)

机构地区：[1]河南中医药大学第一临床医学院肾脏疾病的防治与研究教研室,郑州450008 [2]郑州大学药学院 [3]河南省人民医院肾内科 [4]河南中医药大学第一附属医院泌尿外与肾移植科 [5]华中阜外医院肾内科

出　　处：《山西医科大学学报》2020年第9期955-962,共8页Journal of Shanxi Medical University

基　　金：河南省医学科技攻关计划省部共建项目(SBGJ2018062)。

摘　　要：目的利用代谢图谱的差异,寻找经皮冠状动脉介入治疗(PCI)术后出现肾小管功能障碍患者的尿液代谢标志物。方法筛选PCI术后6 h出现肾小管功能障碍的患者30例,收集其PCI术前尿液样本为对照组,PCI术后6 h尿液样本为观察组。采用超高效液相色谱-质谱联技术分析尿液样本,运用正交偏最小二乘判别分析(OPLS-DA)模式对代谢数据进行分析。结果与对照组相比,观察组尿液中α1-MG、NAG、Cys-C明显升高,差异有统计学意义(P<0.05)。代谢分析模型建立成功,具有较好的稳定性及可预测性且不存在过拟合现象。与对照组相比,观察组尿液样本鉴定出16种潜在生物标志物:L-鸟氨酸、油酸酰胺、D-组氨酸、对羟基苯乳酸、乙酰蛋氨酸、N-(2-呋喃甲酰基)甘氨酸、胆固醇月桂酸酯、胆酸、1-甲基鸟嘌呤、L-氢化乳清酸、高香草酸、α-酮基异己酸、3β-羟基-D5-胆烯酸、腺嘌呤、棕榈酸、十五烷酸,其中L-鸟氨酸的含量显著增加、D-组氨酸的含量显著降低,且分别参与潜在目标代谢通路中的精氨酸与脯氨酸代谢、组氨酸代谢(Impact>0.10)。结论造影后肾小管功能出现障碍可能与组氨酸代谢、精氨酸与脯氨酸代谢紊乱相关。造影后肾小管功能障碍的程度可能与鸟氨酸的含量呈正相关,与组氨酸的含量呈负相关。鸟氨酸和组氨酸可能作为造影剂诱导肾小管功能障碍的潜在生物标志物,助力识别造影剂急性肾损伤(contrast-induced acute kidney injury,CI-AKI)高危患者、预警CI-AKI。Objective To screen the urinary metabolic markers with renal tubular dysfunction after percutaneous coronary intervention(PCI)using the differences in metabolic profiles.Methods Thirty patients who developed tubular dysfunction 6 h after PCI were screened.The urine samples before PCI served as control group,and the urine samples 6 h after PCI were collected as observation group.The metabolic profiles of urine specimens from the two groups were analyzed by liquid chromatography-mass spectrometry technology,and then the data were analyzed by the orthogonal partial least squares-discriminant analysis(OPLS-DA)mode.Results Compared with control group,the urine levels ofα1-MG,NAG and Cys-C in observation group were significantly increased(P<0.05).The metabolic analysis model was established successfully with good stability and predictability and no overfitting.Compared with control group,there were 16 potential biomarkers in observation group,including L(+)-ornithine,oleamide,D-histidine,Dl-phydroxyphenyllactic acid,N-acetyllmethionine,N-(2-furoyl)glycine,cholesteryl laurate,cholic acid,1-methylguanine,L-hydroorotic acid,homovanillic acid,3-methyl-2-oxovalerate,3β-hydroxy-D5-cholenic acid,adenine,palmitic acid,pentadecanoic acid.Among them,the content of L(+)-ornithine was significantly increased,while D-histidine content was decreased significantly,and they respectively participated in the metabolic pathways of arginine and proline metabolism,histidine metabolism(Impact>0.10).Conclusion Renal tubular dysfunction may be related to the disorders of histidine metabolism,arginine and proline metabolism.The degree of renal tubular dysfunction after angiography may be positively correlated with L(+)-ornithine content and negatively correlated with D-histidine content.L(+)-ornithine and D-histidine may serve as potential biomarkers for contrast agent-induced renal tubular dysfunction,assisting in the identification and early warning of CI-AKI patients at high risk.

关 键 词：肾小管功能障碍 经皮冠状动脉介入治疗 代谢组学 尿液 

分 类 号：R699[医药卫生—泌尿科学]