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孕期和哺乳期母体暴露于空气中的颗粒物会导致大鼠母鼠及其雄性后代出现肾损伤:维生素D在孕期及之后的作用。

Maternal exposure to airborne particulate matter during pregnancy and lactation induces kidney injury in rat dams and their male offspring: the role of vitamin D in pregnancy and beyond.

作者信息

Son Min Hwa, Park Eujin, Yim Hyung Eun, Nam Yoon Jeong, Lee Yu-Seon, Choi Eui Kyung, Jeong Sang Hoon, Lee Ju-Han

机构信息

Department of Pediatrics, Korea University Ansan Hospital, Ansan, Republic of Korea.

Department of Pediatrics, Korea University Guro Hospital, Seoul, Republic of Korea.

出版信息

Kidney Res Clin Pract. 2024 Sep;43(5):648-662. doi: 10.23876/j.krcp.23.106. Epub 2024 Jan 2.

Abstract

BACKGROUND

Little is known about the transgenerational effects of maternal exposure to fine particulate matter (PM2.5) on offspring kidney health. This study investigated the effect of maternal administration of PM2.5 or PM2.5 with vitamin D during pregnancy and lactation on renal injury in rat dams and their offspring.

METHODS

Nine pregnant Sprague-Dawley rats received oral administration of normal saline, airborne PM2.5, or PM2.5 with vitamin D from gestational day 11 to postpartum day 21. Kidneys of rat dams (n = 3 for each group) and their male offspring (n = 5 for each group) were taken for analysis on postpartum or postnatal day 21.

RESULTS

Maternal PM2.5 exposure increased glomerular damage, tubulointerstitial injury, and cortical macrophage infiltration in both dams and pups; all increases were attenuated by vitamin D administration. In dam kidneys, PM2.5 increased the protein expression of vitamin D receptor (VDR), klotho, and tumor necrosis factor-α; vitamin D lessened these changes. The expressions of renin, nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear factor-kappa B (NF-κB) p50 decreased in rat dams exposed to PM2.5. In offspring kidneys, exposure to maternal PM2.5 reduced the expression of VDR, renin, angiotensin-converting enzyme (ACE), Nrf2, and NF-κB p50, but increased cytochrome P450 24A1 expression. Maternal vitamin D administration with PM2.5 enhanced VDR, ACE, and NF-κB p50 activities in pup kidneys.

CONCLUSION

PM2.5 exposure during nephrogenesis may exert transgenerational renal impairment, and maternal vitamin D intake could attenuate PM2.5-induced kidney damage in mothers and their offspring.

摘要

背景

关于孕期母亲暴露于细颗粒物(PM2.5)对后代肾脏健康的跨代影响,人们了解甚少。本研究调查了孕期和哺乳期母亲给予PM2.5或PM2.5与维生素D对大鼠母鼠及其后代肾损伤的影响。

方法

9只怀孕的斯普拉格-道利大鼠从妊娠第11天至产后第21天接受口服生理盐水、空气中的PM2.5或PM2.5与维生素D。在产后或出生后第21天取大鼠母鼠(每组n = 3)及其雄性后代(每组n = 5)的肾脏进行分析。

结果

母亲暴露于PM2.5会增加母鼠和幼崽的肾小球损伤、肾小管间质损伤和皮质巨噬细胞浸润;给予维生素D可减轻所有这些增加。在母鼠肾脏中,PM2.5增加了维生素D受体(VDR)、klotho和肿瘤坏死因子-α的蛋白表达;维生素D减轻了这些变化。暴露于PM2.5的大鼠母鼠中肾素、核因子红细胞2相关因子2(Nrf2)和核因子-κB(NF-κB)p50的表达降低。在后代肾脏中,暴露于母亲的PM2.5会降低VDR、肾素、血管紧张素转换酶(ACE)、Nrf2和NF-κB p50的表达,但会增加细胞色素P450 24A1的表达。母亲给予PM2.5的同时补充维生素D可增强幼崽肾脏中VDR、ACE和NF-κB p50的活性。

结论

肾发生期暴露于PM2.5可能会产生跨代肾损伤,母亲摄入维生素D可减轻PM2.5对母亲及其后代肾脏的损害。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63b1/11467365/4ac01ed77fa3/j-krcp-23-106f1.jpg

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