亲代低蛋白饮食小鼠后代肾功能障碍的早期代谢和血液动力学指标

IF 2.4 Q1 PEDIATRICS
Fabiola Diniz, Francesca Edgington-Giordano, Samir S El-Dahr, Giovane G Tortelote
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引用次数: 0

摘要

背景:父母营养不良,尤其是低蛋白饮食(LPD),会在婴儿出生时导致少肾病,并使后代日后易患高血压和慢性肾病。成人肾病的发病因遗传和环境因素而异,肾功能的亚临床改变往往被忽视。本研究旨在检测低蛋白饮食小鼠后代肾功能显著下降前肾脏形态的变化:我们结合使用组织学分析、肾脏代谢和血液动力学面板评估以及线性判别分析(LDA)和主成分分析(PCA)等先进的统计技术,研究了母体低蛋白饮食(LPD)对肾脏发育和功能的初步影响。我们的研究利用了高血压发病前喂食低蛋白饮食(LPD)或正常蛋白饮食(NPD)的 F0 亲本的 12 周大 F1 小鼠:结果:喂食低蛋白饮食(LPD)的亲代(F0 代)的后代(F1 代)从出生到 20 岁体重一直下降。与喂食 NPD 的亲代 F1 后代相比,肾脏重量也有所减少。12 周龄时,体重恢复正常,但肾脏重量仍然很低。喂食LPD的亲本的后代肾脏形态异常,包括肾小管扩张、少肾病和充满液体的囊肿,并且随着年龄的增长而恶化。12 周时进行的肾脏代谢面板分析显示,尿白蛋白、血浆肌酐、平均尿素和 BUN 浓度略有上升,但上升幅度一致。虽然没有观察到血液动力学变量的明显变化,但有 2/12 只小鼠(均为雄性)的收缩压发生了变化,这表明在将 F1 小鼠与喂食两种食物的 F0 小鼠进行比较时,存在性别特异性效应。总体而言,肾脏代谢变化与亲代LPD密切相关:我们的研究结果表明,在血压发生任何可检测到的变化之前,亲代喂养低密度脂蛋白饮食的 F1 代必须积累大量肾脏损伤。我们的研究表明,肾脏代谢功能的微小变化可能预示着早期肾脏损伤,因此不应忽视这些营养不良小鼠的后代以及可能的人类。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Early metabolic and hemodynamic indicators of kidney dysfunction in mice offspring from parental low protein diet.

Background: Parental malnutrition, particularly a low-protein diet (LPD), causes oligonephropathy at birth and predisposes offspring to hypertension and chronic kidney disease later in life. The onset of adult kidney disease varies based on genetics and environmental factors, often with subclinical alterations in kidney function being overlooked. This study aimed to examine changes in kidney morphology before significant kidney function decline in the offspring of mice fed a low-protein diet.

Methods: Using a combination of histological analysis, kidney metabolic and hemodynamic panel assessments, and advanced statistical techniques such as Linear Discriminant Analysis (LDA) and Principal Component Analysis (PCA), we investigated the initial impact of a maternal low-protein diet (LPD) on kidney development and function. Our study utilized 12-week-old F1 mice from F0 parents fed either a low-protein diet (LPD) or a normal-protein diet (NPD) before the onset of hypertension.

Results: The offspring (F1 generation) of parents (F0 generation) fed an LPD show reduced body weight from birth to P20. The kidney weight was also reduced compared to F1 offspring from parents fed an NPD. At 12 weeks of age, body weight normalized, but kidney weight remained low. Offspring of parents fed an LPD displayed abnormal kidney morphology, including dilated tubules, oligonephropathy, and fluid-filled cysts which had worsened with age. A kidney metabolic panel analysis at 12 weeks revealed a slight but consistent increase in urine albumin, plasma creatinine, mean urea, and BUN concentrations. Although no significant changes in hemodynamic variables were observed, 2/12 mice, both males, showed alterations in systolic blood pressure, suggesting sex-specific effects when comparing F1 mice from F0 fed either diet. Overall, kidney metabolic changes were strongly correlated to parental LPD.

Conclusion: Our findings indicate that significant kidney damage must accumulate in the F1 generation from parents fed an LPD before any detectable changes in blood pressure occur. Our study suggests that small variations in kidney metabolic function may point to early kidney damage and should not be overlooked in the offspring of these malnourished mice and likely humans.

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