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目的:探讨实验性单侧肾积水家兔肾脏的代谢组学表型改变,及其与患肾功能和病理学变化的相关性。方法:将18只成年雄性家兔分为实验组(n=12)和对照组(n=6)。实验组动物行单侧输尿管梗阻(UUO)术,对照组行假手术。于梗阻后7d、14d,穿刺收集实验组术侧肾脏积液和对照组膀胱尿液,分别测定H-NMR谱。用核素肾动态显像检测动物肾功能,处死动物取肾脏行病理学检查。结果:实验组家兔UUO建模后,患肾逐渐出现不同程度的炎症反应和组织破坏。尿样中乳酸、氮氧三甲氨、甘氨酸、糖蛋白脂质、丙氨酸、柠檬酸、乙酰乙酸等含量有不同程度的上升,而肌酐、肌酸、β-羟丁酸、尿囊素、马尿酸等则显著下降。主成分分析提示,实验组与对照组的代谢谱有明显差异,造成差异的主要因素是乳酸和肌酐的变化。不同时间各组动物的代谢谱也不相同,与肾脏功能和病理学改变一致。结论:建立实验性肾积水模型能够破坏家兔的肾脏功能和结构,且积液代谢谱与肾积水代谢谱的时间密切相关,代谢组学方法能够较好的反映积水肾脏的受累情况,在梗阻性肾病的研究中前景广阔。
OBJECTIVE: To investigate the changes of metabolomics phenotypes in experimental unilateral hydronephrosis and its correlation with renal function and pathological changes. Methods: 18 adult male rabbits were divided into experimental group (n = 12) and control group (n = 6). The animals in the experimental group underwent unilateral ureteral obstruction (UUO) and the control group underwent sham operation. At 7 days and 14 days after obstruction, H-NMR spectra of the experimental group and the control group were collected by puncture. The radionuclide renal dynamic imaging was used to detect the animal’s kidney function. The animals were sacrificed and the pathological examination of the kidney was performed. Results: After the UUO model was established in the experimental group, different degrees of inflammatory reaction and tissue destruction gradually appeared in the kidney. Urinary samples lactic acid, triamcinolone, glycine, glycoprotein, alanine, citric acid, acetoacetate content increased to varying degrees, and creatinine, creatine, β-hydroxybutyrate, allantoin, Hippuric acid and so significantly decreased. The principal component analysis suggested that there was a significant difference in the metabolic profile between the experimental group and the control group. The main factors causing the difference were the changes of lactate and creatinine. The metabolic profiles of the animals in different groups were also different at different times, which was consistent with the changes of renal function and pathology. Conclusion: The establishment of experimental hydronephrosis model can damage the function and structure of kidney in rabbits, and the fluid metabolite profile is closely related to the time of hydronephrosis, and metabolomics can better reflect the involvement of hydronephrosis , In the study of obstructive nephropathy promising.