Department of Basic Medical Sciences, Faculty of Health Sciences, Durban University of Technology, Durban, South Africa.
Optics and Imaging Centre, Doris Duke Medical Research Institute, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
Eur J Obstet Gynecol Reprod Biol. 2023 May;284:58-65. doi: 10.1016/j.ejogrb.2023.03.012. Epub 2023 Mar 15.
To assess renal injury in an arginine vasopressin (AVP) rodent model of preeclampsia.
Urinary expression of kidney injury molecule-1 (KIM-1), urinary protein and creatinine was determined in rodents (n = 24; pregnant AVP, pregnant saline, non-pregnant AVP and non-pregnant saline), which received a continuous dose of either AVP or saline via subcutaneous mini osmotic pumps for 18 days, using a Multiplex kidney toxicity immunoassay. Renal morphology was assessed using haematoxylin and eosin staining and transmission electron microscopy. The immunolocalization of KIM-1 and podocalyxin was qualitatively evaluated using immunohistochemistry.
Urinary KIM-1 and urinary protein levels were significantly increased in treated vs. untreated rats on gestational days 8 (p < 0.05), 14 (p < 0.001) and 18 (p < 0.001). The pregnant rats displayed a lower trend of creatinine compared to the non-pregnant groups, albeit non-significantly. KIM-1 was immunolocalized in the proximal convoluted tubules in AVP treated vs. untreated groups. In contrast, podocalyxin was weakly immunostained within glomeruli of pregnant AVP treated vs. pregnant untreated rats. Histological evaluation revealed reduced Bowman's space, with some tubular and blood vessel necrosis in the pregnant treated group. Ultrastructural observations included effacement and fusion of podocyte foot processes, glomerular basement membrane abnormalities, podocyte nuclear crenations, mitochondrial oedema and cristae degeneration with cytoplasmic lysis within treated tissue.
Our findings demonstrate region-specific kidney injury particularly glomerular impairment and endothelial injury in AVP-treated rats. The findings highlight the utility of this model in studying the mechanisms driving renal damage in a rodent model of preeclampsia.
评估血管加压素（AVP）在子痫前期啮齿动物模型中的肾损伤。
通过多指标肾毒性免疫测定法，在接受持续皮下微量渗透泵给予 AVP 或生理盐水治疗的 24 只啮齿动物（怀孕 AVP 组、怀孕生理盐水组、非怀孕 AVP 组和非怀孕生理盐水组）中，测定尿肾损伤分子-1（KIM-1）、尿蛋白和肌酐的表达。采用苏木精和伊红染色和透射电镜观察肾形态。使用免疫组织化学定性评估 KIM-1 和足细胞蛋白的免疫定位。
在妊娠第 8 天（p<0.05）、第 14 天（p<0.001）和第 18 天（p<0.001），与未治疗组相比，治疗组的尿 KIM-1 和尿蛋白水平显著升高。与非怀孕组相比，怀孕组的肌酐水平呈下降趋势，但无统计学意义。在 AVP 治疗组与未治疗组中，KIM-1 免疫定位在近端曲管。相反，在怀孕 AVP 治疗组与怀孕未治疗组相比，足细胞蛋白在肾小球中弱免疫染色。组织学评估显示怀孕治疗组的 Bowman 空间减少，伴有一些肾小管和血管坏死。超微结构观察包括足细胞足突的融合和消失、肾小球基底膜异常、足细胞核皱缩、线粒体水肿和嵴变性以及细胞质溶解。
我们的研究结果表明，AVP 治疗的大鼠存在特定区域的肾脏损伤，特别是肾小球损伤和内皮损伤。这些发现突出了该模型在研究子痫前期啮齿动物模型中肾脏损伤机制方面的应用价值。
