Is renal dysfunction amplified in an arginine vasopressin induced rat model of preeclampsia?

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS ACS Applied Bio Materials Pub Date : 2024-06-07 DOI:10.1016/j.repbio.2024.100910

Sapna Ramdin , Thajasvarie Naicker , Sooraj Baijnath , Nalini Govender

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Abstract

Renal dysfunction is important in preeclampsia (PE) pathophysiology and has not been fully explored in the arginine vasopressin (AVP) rat model of PE. This study aimed to determine kidney toxicity associated with this model. Female Sprague Dawley rats (n = 24) were subcutaneously infused with AVP or saline for 18 days. Urine samples (GD8, 14 and 18) were used to determine the levels of albumin, VEGF-A, clusterin, NGAL/Lipocalin-2, KIM-1, cystatin C, TIMP-1, β2M and OPN via Multiplex ELISAs. Albumin, and NGAL/lipocalin-2 were significantly elevated in the PAVP vs PS group on GD14 and GD18 (p < 0.001) respectively. VEGF-A significantly decreased in the pregnant vs non-pregnant groups on GD14 and 18 (p < 0.001). Clusterin (p < 0.001) and OPN (p < 0.05) were significantly higher in the PAVP vs PS group on GD18. Cystatin C and KIM-1 are significantly upregulated in the PAVP vs PS groups throughout gestation (p < 0.05). β2M is significantly elevated in the PAVP vs PS group on GD14 and 18 (p < 0.05). AVP elevated the urinary levels of the kidney injury biomarkers and replicated the renal dysfunction associated with PE development. Our findings confirm the potential applications of this model in studying the mechanisms underlying renal damage in PE.

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在精氨酸加压素诱导的子痫前期大鼠模型中，肾功能障碍是否会加重？

肾功能障碍在子痫前期（PE）病理生理学中非常重要，但在精氨酸加压素（AVP）大鼠子痫前期模型中尚未得到充分探讨。本研究旨在确定与该模型相关的肾毒性。雌性 Sprague Dawley 大鼠（n = 24）皮下注射 AVP 或生理盐水 18 天。尿液样本（GD8、14 和 18）通过多重 ELISAs 检测白蛋白、血管内皮生长因子-A、集束蛋白、NGAL/脂联素-2、KIM-1、胱抑素 C、TIMP-1、β2M 和 OPN 的水平。在 GD14 和 GD18，PAVP 组与 PS 组相比，白蛋白和 NGAL/Lipocalin-2 分别显著升高（p < 0.001）。在 GD14 和 18 期，妊娠组与未妊娠组相比，VEGF-A 明显下降（p <0.001）。在 GD18，PAVP 组与 PS 组相比，Clusterin（p < 0.001）和 OPN（p < 0.05）明显升高。在整个妊娠期，胱抑素 C 和 KIM-1 在 PAVP 组和 PS 组明显上调（p < 0.05）。在 GD14 和 18，PAVP 组与 PS 组相比，β2M 明显升高（p < 0.05）。AVP 升高了尿液中肾损伤生物标志物的水平，并复制了与 PE 发展相关的肾功能障碍。我们的研究结果证实了该模型在研究 PE 肾损伤机制方面的潜在应用。

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