School of Veterinary and Life Sciences, Murdoch University, 90 South Street, Murdoch, WA 6150, Australia; Separation Science and Metabolomics Laboratory, Murdoch University, 90 South Street, Murdoch, WA 6150, Australia.
School of Veterinary and Life Sciences, Murdoch University, 90 South Street, Murdoch, WA 6150, Australia; Separation Science and Metabolomics Laboratory, Murdoch University, 90 South Street, Murdoch, WA 6150, Australia.
J Chromatogr B Analyt Technol Biomed Life Sci. 2019 Jun 15;1118-1119:25-32. doi: 10.1016/j.jchromb.2019.04.021. Epub 2019 Apr 12.
Polycystic kidney disease (PKD) encompasses a spectrum of inherited disorders that lead to end-stage renal disease (ESRD). There is no cure for PKD and current treatment options are limited to renal replacement therapy and transplantation. A better understanding of the pathobiology of PKD is needed for the development of new, less invasive treatments. The Lewis Polycystic Kidney (LPK) rat phenotype has been characterized and classified as a model of nephronophthisis (NPHP9, caused by mutation of the Nek8 gene) for which polycystic kidneys are one of the main pathologic features. The aim of this study was to use a GC-MS-based untargeted metabolomics approach to determine key biochemical changes in kidney and liver tissue of the LPK rat. Tissues from 16-week old LPK (n = 10) and Lewis age- and sex-matched control animals (n = 11) were used. Principal component analysis (PCA) distinguished signal corrected metabolite profiles from Lewis and LPK rats for kidney (PC-1 77%) and liver (PC-1 46%) tissue. There were marked differences in the metabolite profiles of the kidney tissues with 122 deconvoluted features significantly different between the LPK and Lewis strains. The metabolite profiles were less marked between strains for liver samples with 30 features significantly different. Five biochemical pathways showed three or more significantly altered metabolites: transcription/translation, arginine and proline metabolism, alpha-linolenic and linoleic acid metabolism, the citric acid cycle, and the urea cycle. The results of this study validate and complement the current literature and are consistent with the understood pathobiology of PKD.
多囊肾病（PKD）涵盖了一系列导致终末期肾病（ESRD）的遗传性疾病。目前尚无治愈 PKD 的方法，现有的治疗选择仅限于肾脏替代治疗和移植。为了开发新的、侵入性更小的治疗方法，需要更好地了解 PKD 的病理生物学。Lewis 多囊肾病（LPK）大鼠表型已被表征，并被归类为肾病（NPHP9，由 Nek8 基因突变引起）的模型，多囊肾是其主要病理特征之一。本研究旨在使用基于 GC-MS 的非靶向代谢组学方法来确定 LPK 大鼠肾脏和肝脏组织中的关键生化变化。使用 16 周龄 LPK（n=10）和 Lewis 年龄和性别匹配的对照动物（n=11）的组织。主成分分析（PCA）区分了来自 Lewis 和 LPK 大鼠的肾脏（PC-1 77%）和肝脏（PC-1 46%）组织的信号校正代谢物图谱。LPK 和 Lewis 大鼠的肾脏组织代谢物图谱存在明显差异，122 个去卷积特征显著不同。与肝脏样本相比，菌株之间的代谢物图谱差异较小，有 30 个特征显著不同。有五个生化途径显示三个或更多代谢物明显改变：转录/翻译、精氨酸和脯氨酸代谢、α-亚麻酸和亚油酸代谢、柠檬酸循环和尿素循环。本研究的结果验证和补充了当前的文献，并与 PKD 的已知病理生物学一致。
