Kollenkirchen U, Walters M R, Fox J
Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana 70112.
Am J Physiol. 1991 Mar;260(3 Pt 1):E447-52. doi: 10.1152/ajpendo.1991.260.3.E447.
The hypocalcemia that accompanies vitamin D deficiency is a major obstacle to proper interpretation of the role(s) of vitamin D metabolites in Ca-sensitive tissues. This paper describes the development and complete characterization of a dietary regimen with which normocalcemia was maintained in rats throughout the development of vitamin D deficiency. Normal weanling rats were fed diets containing 0.8% Ca, 0.5% P, and vitamin D3 (group A), or vitamin D-deficient diets containing 0.8% Ca and 0.5% P (group B); 2.0% Ca and 1.25% P (group C); or 2.0% Ca, 1.25% P, and 20% lactose (group D) for 19 wk. Group D rats were normocalcemic and normophosphatemic with normal parathyroid hormone (PTH) levels throughout the study. In contrast, from 4-19 diet wk, groups B and C were hypocalcemic with elevated PTH. Initially, plasma 25-hydroxyvitamin D3 [25(OH)D3] levels decreased most rapidly, and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] levels decreased least rapidly in group B rats, such that plasma 25(OH)D3 levels were reduced to 200-300 pg/ml before a decrease in 1,25(OH)2D3 levels was observed. However, vitamin D metabolite levels were similar in groups B, C, and D from 4-19 wk. Duodenal active Ca transport mirrored changes in plasma 1,25(OH)2D3 levels and was abolished after 10 wk. The results also suggested that vitamin D may not be necessary for normal bone mineralization since tibia mineral content and plasma alkaline phosphatase levels were similar in normocalcemic groups A and D throughout the study.
维生素D缺乏伴随的低钙血症是正确解读维生素D代谢产物在钙敏感组织中作用的主要障碍。本文描述了一种饮食方案的制定及全面特性,通过该方案在大鼠维生素D缺乏的整个发展过程中维持血钙正常。正常断奶大鼠喂食含0.8%钙、0.5%磷和维生素D3的饮食(A组),或含0.8%钙和0.5%磷的维生素D缺乏饮食(B组);2.0%钙和1.25%磷(C组);或2.0%钙、1.25%磷和20%乳糖的饮食(D组),持续19周。在整个研究过程中,D组大鼠血钙和血磷正常,甲状旁腺激素(PTH)水平正常。相比之下,从饮食第4 - 19周,B组和C组血钙过低,PTH升高。最初,B组大鼠血浆25 - 羟基维生素D3 [25(OH)D3]水平下降最快,1,25 - 二羟基维生素D3 [1,25(OH)2D3]水平下降最慢,以至于在观察到1,25(OH)2D3水平下降之前,血浆25(OH)D3水平已降至200 - 300 pg/ml。然而,在第4 - 19周,B、C和D组的维生素D代谢产物水平相似。十二指肠活性钙转运反映了血浆1,25(OH)2D3水平的变化,并在10周后消失。结果还表明,正常骨矿化可能不需要维生素D,因为在整个研究过程中,血钙正常的A组和D组胫骨矿物质含量和血浆碱性磷酸酶水平相似。