Ureteral obstruction will lead clinically to hydronephrosis, which may further develop into partial or complete loss of kidney function and even cause permanent histological damage. However, there is little knowledge of metabolic responses during the obstructed process and its recoverability. In this study, a complete unilateral ureteral obstruction (CUUO) model was established in the rabbit, and ¹H NMR-based metabolomic analysis of urine was used to reveal the metabolic perturbations in rabbits caused by CUUO and the metabolic recovery after the CUUO was relieved. Univariate and multivariate statistical analyses were used to identify metabolic characteristics. The gradually decreased levels of 3-hydroxykynurenine, 3-methylhistidine, creatinine, guanidoacetate, meta- and para-hydroxyphenylacetate, and phenylacetylglycine and the gradually increased levels of acetate, alanine, citrate, glycine, lactate, and methionine in urine could be regarded as potential biomarkers for the occurrence and severity of ureteral obstruction. And the reduced levels of 3-methylhistidine, creatinine, guanidoacetate, hippurate, meta-hydroxyphenylacetate, and methylguanidine and the elevated levels of 2-aminoisobutyrate, acetylcholine, citrate, lactate, lysine, valine, and α-ketoglutarate in urine compared with the obstructed level could characterize the metabolic recovery of ureteral obstruction. Our results depicted the disturbed biochemical pathways involved in ureteral obstruction and demonstrated the practicability of recovering renal functions for the patients with severe hydronephrosis in clinical practice by removing causes for obstruction.

中文翻译：

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兔尿液对单侧输尿管梗阻的发生和缓解的代谢反应

输尿管阻塞在临床上会导致肾积水，这可能进一步发展为部分或完全丧失肾功能，甚至造成永久性组织学损害。但是，关于阻塞过程中的代谢反应及其可恢复性的知识很少。在这项研究中，在兔中建立了一个完整的单侧输尿管梗阻（CUUO）模型，并使用基于¹ H NMR的尿液代谢组学分析揭示了由CUUO引起的兔体内代谢紊乱以及CUUO缓解后的代谢恢复。使用单变量和多变量统计分析来识别代谢特征。3-羟基犬尿氨酸，3-甲基组氨酸，肌酐，胍基乙酸酯，间-和-的水平逐渐降低第-hydroxyphenylacetate，和phenylacetylglycine和乙酸，丙氨酸，柠檬酸，甘氨酸，乳酸根，和蛋氨酸在尿的逐渐增加的水平可以被视为对输尿管梗阻的发生和严重程度潜在生物标志物。和3-甲基，肌酐，guanidoacetate，马尿酸盐，水平降低元尿中的β-羟基苯乙酸和甲基胍以及尿液中2-氨基异丁酸盐，乙酰胆碱，柠檬酸盐，乳酸盐，赖氨酸，缬氨酸和α-酮戊二酸的水平升高与阻塞水平相比，可表征输尿管阻塞的代谢恢复。我们的结果描述了与输尿管梗阻有关的生化途径紊乱，并证明了在临床实践中通过消除梗阻原因可恢复严重肾积水患者的肾功能的实用性。