Song Yurong, Kato Shigeaki, Fleet James C
Interdepartmental Nutrition Program, Purdue University, West Lafayette, IN 47907, USA.
J Nutr. 2003 Feb;133(2):374-80. doi: 10.1093/jn/133.2.374.
To study the role of calbindin D(9k) (CaBP) and epithelial calcium channel ECaC2 in intestinal calcium (Ca) absorption, vitamin D receptor knockout (KO) and wild-type (WT) mice were fed either 0.5% Ca or a 2.0% Ca rescue diet starting at 21 d of age. Ca absorption and parameters involved in this process were measured at 60 or 90 d of age. Compared with WT, KO mice fed the 0.5% Ca diet had higher plasma parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], and lower plasma Ca and insulin-like growth factor-I (IGF-I). Duodenal Ca absorption (% Ca absorbed) in KO mice was reduced 71% relative to WT mice and was associated with 55% lower CaBP mRNA, 47% lower CaBP protein and 95% lower ECaC2 mRNA levels. Compared with WT mice, the percentage of Ca absorbed in KO mice fed the 0.5% Ca diet was inappropriately low for the level of duodenal CaBP. The 2% Ca rescue diet normalized plasma Ca, prevented osteomalacia, increased growth and plasma IGF-I levels, but did not normalize plasma PTH or 1,25(OH)(2)D(3) in KO mice. In addition, the relationship between CaBP protein and the percentage of Ca absorbed was normalized, whereas ECaC2 mRNA fell to near zero. Our data demonstrate that higher CaBP levels do not ensure high rates of duodenal Ca absorption and that transcellular Ca absorption can occur even when ECaC2 gene expression is very low. In addition, our data suggest that the 2% Ca diet promotes a vitamin D receptor-independent anabolic effect on bone formation and calcium absorption, leading to improved calcium balance even in the presence of high PTH levels.
为研究钙结合蛋白D(9k)(CaBP)和上皮钙通道ECaC2在肠道钙吸收中的作用，维生素D受体基因敲除(KO)小鼠和野生型(WT)小鼠自21日龄起分别喂食0.5%钙或2.0%钙的挽救饮食。在60或90日龄时测量钙吸收及此过程中涉及的参数。与野生型小鼠相比，喂食0.5%钙饮食的基因敲除小鼠血浆甲状旁腺激素(PTH)和1,25-二羟维生素D(3)[1,25(OH)2D(3)]水平较高，而血浆钙和胰岛素样生长因子-I(IGF-I)水平较低。基因敲除小鼠十二指肠钙吸收(吸收的钙百分比)相对于野生型小鼠降低了71%，且与CaBP mRNA水平降低55%、CaBP蛋白水平降低47%和ECaC2 mRNA水平降低95%相关。与野生型小鼠相比，喂食0.5%钙饮食的基因敲除小鼠的钙吸收百分比相对于十二指肠CaBP水平过低。2%钙的挽救饮食使基因敲除小鼠的血浆钙正常化，预防了骨软化症，增加了生长和血浆IGF-I水平，但未使基因敲除小鼠的血浆PTH或1,25(OH)2D(3)正常化。此外，CaBP蛋白与钙吸收百分比之间的关系正常化，而ECaC2 mRNA降至接近零。我们的数据表明，较高的CaBP水平并不能确保十二指肠钙的高吸收率，并且即使ECaC2基因表达非常低时也可发生跨细胞钙吸收。此外，我们的数据表明，2%钙的饮食对骨形成和钙吸收具有不依赖维生素D受体的合成代谢作用，即使在PTH水平较高的情况下也能改善钙平衡。
