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常染色体隐性多囊肾病大鼠模型囊肿液的电解质和代谢物组成

Electrolyte and metabolite composition of cystic fluid from a rat model of ARPKD.

作者信息

Klemens Christine A, Fedoriuk Mykhailo, Semenikhina Marharyta, Stefanenko Mariia, Zietara Adrian, Levchenko Vladislav, Dissanayake Lashodya V, Palygin Oleg, Staruschenko Alexander

机构信息

Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL, USA.

Hypertension and Kidney Research Center, University of South Florida, Tampa, FL, USA.

出版信息

Commun Biol. 2025 Feb 13;8(1):230. doi: 10.1038/s42003-025-07631-w.

Abstract

Fluid-filled cysts are the key feature of polycystic kidney disease, which eventually leads to renal failure. We analyzed the composition of cyst fluid from a rat model of autosomal recessive polycystic kidney disease, the PCK rat, and identified sexual differences. Our results demonstrate that the ion composition of cyst fluid differs from that of urine or plasma. Untargeted metabolomics combined with transcriptomic data identified tryptophan metabolism, enzyme metabolism, steroid hormone biosynthesis, and fatty acid metabolism as pathways differing between male and female PCK rats. We quantified 42 amino acids in the cyst fluid (PCK only), plasma, and urine of male and female PCK rats and Sprague Dawley rats. Taurine was the most concentrated amino acid present in the cyst fluid, and PCK rat urinary taurine excretion was over 3-fold greater than Sprague Dawley rats. Understanding the composition of cyst fluid provides valuable insights into disease pathophysiology and may help identify potential dietary or pharmacological interventions to mitigate disease progression and improve patient outcomes.

摘要

充满液体的囊肿是多囊肾病的关键特征,最终会导致肾衰竭。我们分析了常染色体隐性多囊肾病大鼠模型(PCK大鼠)囊肿液的成分,并确定了性别差异。我们的结果表明,囊肿液的离子组成不同于尿液或血浆。非靶向代谢组学结合转录组数据确定,色氨酸代谢、酶代谢、类固醇激素生物合成和脂肪酸代谢是雄性和雌性PCK大鼠之间存在差异的途径。我们对雄性和雌性PCK大鼠以及斯普拉格·道利大鼠的囊肿液(仅PCK大鼠)、血浆和尿液中的42种氨基酸进行了定量分析。牛磺酸是囊肿液中含量最高的氨基酸,PCK大鼠尿中牛磺酸排泄量比斯普拉格·道利大鼠高3倍以上。了解囊肿液的成分有助于深入了解疾病的病理生理学,并可能有助于确定潜在的饮食或药物干预措施,以减轻疾病进展并改善患者预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97a6/11825955/6e647d471cc9/42003_2025_7631_Fig1_HTML.jpg

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