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由于母体维生素 D 缺乏导致促血管生成和抗血管生成因子失衡会引起肾脏微血管改变,从而影响成年后的肾脏功能。

Imbalance of Pro- and Anti-Angiogenic Factors Due to Maternal Vitamin D Deficiency Causes Renal Microvasculature Alterations Affecting the Adult Kidney Function.

机构信息

Department of Physiology of Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo 14049-900, Brazil.

Department of Internal Medicine of Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo 14049-900, Brazil.

出版信息

Nutrients. 2019 Aug 16;11(8):1929. doi: 10.3390/nu11081929.

DOI:10.3390/nu11081929
PMID:31426337
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6723450/
Abstract

Vitamin D (Vit.D) is involved in cellular proliferation and differentiation and regulation of the renin gene, which are important aspects of nephrogenesis and quiescence of renal health in adulthood. This study evaluated the angiogenic mechanisms involved in long term renal disturbances induced by Vit.D deficiency persistent in adulthood in rats. First-generation male Hannover offspring from mothers fed either a control diet (control group, CG) or Vit.D-deficient diet (Vit.D- group) were evaluated. Systolic blood pressure (SBP) was measured monthly during the first 6 months after birth, and blood and urine samples were collected to evaluate renal function. Nitric oxide (NO), angiotensin II (ANGII), parathyroid hormone (PTH), calcium, and Vit.D were measured. The kidneys were then removed for morphometric, NO, immunohistochemical, and Western blot studies. We evaluated the expression of vascular growth factor (VEGF) and angiopoietins 1 and 2 and their receptors since this intrinsic renal axis is responsible for endothelial quiescence. Compared to CG, the Vit.D- group presented higher SBP, ANG II plasma levels, renin expression, and AT1 receptor expression levels. Capillary rarefaction was observed, as well as an imbalance between pro- and anti-angiogenic factors. Collectively, the present findings support the role of Vit.D for maintaining the integrity of renal microcirculation.

摘要

维生素 D(Vit.D)参与细胞增殖和分化以及肾素基因的调节,这是肾发生和成年期肾脏健康静息的重要方面。本研究评估了成年期持续维生素 D 缺乏引起的长期肾脏紊乱所涉及的血管生成机制。评估了第一代雄性汉诺威后代,这些后代来自喂食对照饮食(对照组,CG)或维生素 D 缺乏饮食(Vit.D-组)的母亲。在出生后的前 6 个月内每月测量收缩压(SBP),收集血液和尿液样本以评估肾功能。测量了一氧化氮(NO)、血管紧张素 II(ANGII)、甲状旁腺激素(PTH)、钙和 Vit.D。然后取出肾脏进行形态计量学、NO、免疫组织化学和 Western blot 研究。由于这个内在的肾脏轴负责内皮细胞静息,我们评估了血管生长因子(VEGF)和血管生成素 1 和 2 及其受体的表达。与 CG 相比,Vit.D-组的 SBP、ANG II 血浆水平、肾素表达和 AT1 受体表达水平更高。观察到毛细血管稀疏,以及促血管生成和抗血管生成因子之间的失衡。总之,这些发现支持了 Vit.D 维持肾脏微循环完整性的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e182/6723450/716073a9d38f/nutrients-11-01929-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e182/6723450/402f10efd440/nutrients-11-01929-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e182/6723450/98d3c4937746/nutrients-11-01929-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e182/6723450/44e5bc7f9f66/nutrients-11-01929-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e182/6723450/dabffd8ada72/nutrients-11-01929-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e182/6723450/716073a9d38f/nutrients-11-01929-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e182/6723450/402f10efd440/nutrients-11-01929-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e182/6723450/98d3c4937746/nutrients-11-01929-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e182/6723450/44e5bc7f9f66/nutrients-11-01929-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e182/6723450/dabffd8ada72/nutrients-11-01929-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e182/6723450/716073a9d38f/nutrients-11-01929-g005.jpg

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