Park Eujin, Yim Hyung-Eun, Son Min-Hwa, Nam Yoon-Jeong, Lee Yu-Seon, Jeong Sang-Hoon, Lee Ju-Han
Department of Pediatrics, Korea University Guro Hospital, 148, Gurodong-ro, Guro-gu, Seoul 08308, Republic of Korea.
Department of Pediatrics, Korea University Ansan Hospital, 123, Jeokgeum-ro, Danwon-gu, Ansan-si 15355, Republic of Korea.
Biomedicines. 2025 May 10;13(5):1166. doi: 10.3390/biomedicines13051166.
: This study aimed to investigate the long-term effects of maternal exposure to fine particulate matter (PM) with or without vitamin D supplementation on the renal microvasculature in adult rat offspring. : Pregnant Sprague-Dawley rats were exposed to normal saline, PM, and PM with vitamin D for one month during nephrogenesis. Male offspring kidneys were taken for analyses on postnatal day 56. : Adult offspring rats exposed to maternal PM exhibited lower body weights and greater glomerular and tubular injury scores compared to control rats. Semi-quantitative analysis revealed a significant reduction in glomerular and peritubular capillary endothelial cells, along with a decrease in the number of glomeruli in the PM group. Maternal vitamin D supplementation reduced these changes. In offspring rats exposed to maternal PM, intrarenal expression of renin, angiotensin-converting enzyme (ACE), cytochrome P450 27B1, and vascular endothelial growth factor-A (VEGF-A) increased, while expression of the vitamin D receptor, Klotho, VEGF receptor 2, angiopoietin-1, and Tie-2 decreased. Maternal vitamin D supplementation restored VEGF receptor 2 and angiopoietin-1 activities and reduced ACE and VEGF-A protein expression in adult offspring kidneys. : Early-life exposure to PM may lead to long-term alterations in renal microvasculature and nephron loss. Maternal vitamin D supplementation during renal development can ameliorate PM-induced capillary rarefaction and nephron loss in the kidneys of adult offspring.
本研究旨在调查孕期暴露于细颗粒物（PM）且补充或未补充维生素D对成年大鼠子代肾微血管系统的长期影响。在肾发生期，将怀孕的斯普拉格-道利大鼠暴露于生理盐水、PM以及补充维生素D的PM环境中1个月。在出生后第56天取雄性子代的肾脏进行分析。与对照大鼠相比，暴露于母体PM环境的成年子代大鼠体重较低，肾小球和肾小管损伤评分更高。半定量分析显示，PM组肾小球和肾小管周围毛细血管内皮细胞显著减少，同时肾小球数量减少。母体补充维生素D可减轻这些变化。在暴露于母体PM的子代大鼠中，肾内肾素、血管紧张素转换酶（ACE）、细胞色素P450 27B1和血管内皮生长因子-A（VEGF-A）的表达增加，而维生素D受体、Klotho、VEGF受体2、血管生成素-1和Tie-2的表达减少。母体补充维生素D可恢复成年子代肾脏中VEGF受体2和血管生成素-1的活性，并降低ACE和VEGF-A蛋白的表达。早期暴露于PM可能导致肾微血管系统的长期改变和肾单位丢失。在肾脏发育期间母体补充维生素D可改善PM诱导的成年子代肾脏毛细血管稀疏和肾单位丢失。
