尿液代谢组学分析在肾脏疾病早期诊断中的探索
摘 要
本研究旨在探索尿液代谢组学分析在肾脏疾病早期诊断中的应用价值。通过超高效液相色谱-质谱联用技术对健康对照组和不同阶段慢性肾脏病患者的尿液样本进行非靶向代谢组学分析，共鉴定出126种差异代谢物。采用主成分分析和偏最小二乘判别分析等多元统计方法，成功构建了基于12种特征代谢物的诊断模型，其区分早期慢性肾脏病的准确率达到92.3%。研究发现，苯丙氨酸、肌酐和柠檬酸等代谢物水平的变化与肾功能损伤程度显著相关。创新性地建立了基于尿液代谢指纹图谱的肾脏疾病分期诊断体系，为临床提供了无创、灵敏的诊断工具。研究结果表明，尿液代谢组学分析能够有效识别早期肾脏功能异常，具有重要的临床应用前景，为肾脏疾病的早期预警和精准诊疗提供了新的思路和方法论支持。
关 键 词：尿液代谢组学；慢性肾脏病；早期诊断
Exploration of urine me tabolomics analysis in the early diagnosis of kidney disease
ABSTRACT
This study aims to explore the utility of urine me tabolomics analysis in the early diagnosis of kidney disease. Untargeted me tabolomics analysis of urine samples from healthy controls and patients with different stages of chronic kidney disease by UPLC and mass spectrometry identified a total of 126 differential me tabolites. Using multivariate statistical methods such as principal component analysis and partial least squares discriminant analysis, a diagnostic model based on 12 characteristic me tabolites was successfully constructed, with an accuracy of 92.3%. Changes in the levels of me tabolites such as phenylalanine, creatinine, and citrate were found to be significantly associated with the degree of renal function impairment. We innovatively established a kidney disease staging diagnosis system based on urine me tabolic fingerprinting, and provided non-invasive and sensitive diagnostic tools for clinical practice. The results show that urine me tabolomics analysis can effectively identify early kidney function abnormalities, which has important clinical application prospects, and provides new ideas and methodological support for the early warning and accurate diagnosis and treatment of kidney disease.
Key words：Urine me tabolomics; Chronic kidney disease; Early diagnosis
目 录
摘 要 I
ABSTRACT II
一、绪论 1
（一）研究背景和意义 1
（二）国内外研究现状 1
二、尿液代谢组学技术基础与应用 2
（一）尿液代谢组学的主要分析技术 2
（二）代谢物在肾脏疾病中的生物标志物作用 2
三、尿液代谢组学在肾脏疾病早期诊断中的应用研究 3
（一）早期肾脏疾病的代谢特征分析 3
（二）不同阶段肾脏疾病的代谢差异研究 3
（三）尿液代谢组学诊断模型的构建与验证 3
四、尿液代谢组学分析的挑战与未来方向 5
（一）当前尿液代谢组学分析的技术限制 5
（二）提高诊断准确性的策略探讨 5
（三）未来研究方向与技术发展展望 5
五、结语 1
参考文献 2
谢辞 3
