Hernández A, Concepción M T, Rodríguez M, Salido E, Torres A
Servicio de Nefrología, Hospital Universitario de Canarias, Universidad de La Laguna, Tenerife, Spain.
Kidney Int. 1996 Dec;50(6):1872-8. doi: 10.1038/ki.1996.508.
Phosphorus retention favors secondary hyperparathyroidism by decreasing calcitriol synthesis and serum calcium levels. However, a direct effect of high extracellular phosphorus on parathyroid (PTH) function, gene expression, and cell proliferation is still controversial. Normal rats were fed standard (St; 0.6% calcium, 0.6% phosphorus) or high phosphate (HP) diet (0.6% calcium, 1.2% phosphorus) for 18 days. To rule out transient decreases in serum calcium or calcitriol levels, sets of animals were sacrificed at different time periods after the last feeding (2, 4, 8, 12 or 24 hr). The HP diet led to hyperphosphatemia and secondary hyperparathyroidism and maximum differences in PTH levels were observed eight hours after feeding (St 29.4 +/- 15 vs. HP 87.9 +/- 56 pg/ml, mean +/- SD; P = 0.01). High levels induced by the HP diet prevented both hypocalcemia and low calcitriol levels at each study point. The HP diet also promoted a significant increase of PTH mRNA levels that peaked about eight hours after feeding (100% increase). This was confirmed at the cellular level by in situ hybridization. Parathyroid glands from animals fed the HP diet showed a 25% increase in volume with respect to the St diet (P = 0.01), and a typical pattern of hyperplasia was found. Parathyroid vitamin D receptor (VDR) mRNA levels were not modified by the HP diet. In conclusion, parathyroid gene expression per cell and parathyroid cell hyperplasia are stimulated by high dietary phosphorus independently of calcium and calcitriol. This effect is not mediated by alterations in the gene expression of the parathyroid calcitriol receptor. Our findings emphasize the importance of the control of hyperphosphatemia in chronic renal failure patients.
磷潴留通过降低骨化三醇合成和血清钙水平，促进继发性甲状旁腺功能亢进。然而，细胞外高磷对甲状旁腺（PTH）功能、基因表达和细胞增殖的直接作用仍存在争议。将正常大鼠喂食标准（St；0.6%钙，0.6%磷）或高磷（HP）饮食（0.6%钙，1.2%磷）18天。为排除血清钙或骨化三醇水平的短暂下降，在最后一次喂食后的不同时间段（2、4、8、12或24小时）处死动物组。HP饮食导致高磷血症和继发性甲状旁腺功能亢进，喂食后8小时观察到PTH水平的最大差异（St 29.4 +/- 15 vs. HP 87.9 +/- 56 pg/ml，平均值 +/- 标准差；P = 0.01）。HP饮食诱导的高水平在每个研究点都可防止低钙血症和低骨化三醇水平。HP饮食还促进了PTH mRNA水平的显著升高，在喂食后约8小时达到峰值（增加100%）。原位杂交在细胞水平证实了这一点。喂食HP饮食的动物的甲状旁腺相对于St饮食体积增加了25%（P = 0.01），并发现了典型的增生模式。甲状旁腺维生素D受体（VDR）mRNA水平未因HP饮食而改变。总之，高膳食磷可独立于钙和骨化三醇刺激甲状旁腺细胞的基因表达和甲状旁腺细胞增生。这种作用不是由甲状旁腺骨化三醇受体的基因表达改变介导的。我们的研究结果强调了控制慢性肾衰竭患者高磷血症的重要性。
