Ritter C S, Finch J L, Slatopolsky E A, Brown A J
Renal Division, Washington University Medical School, St. Louis, Missouri 63110, USA.
Kidney Int. 2001 Nov;60(5):1737-44. doi: 10.1046/j.1523-1755.2001.00027.x.
Recent evidence points to a relationship between the down-regulation of the calcium-sensing receptor (CaR) and parathyroid cell hyperplasia that is associated with chronic renal failure. It is not known, however, if down-regulation of the CaR precedes, and perhaps initiates, parathyroid cell proliferation, or if a decrease in the expression of the CaR occurs subsequently to hyperplasia or the conditions promoting it. The current study examined the temporal relationship of these two events.
Rats were made uremic by subtotal nephrectomy and were (1) placed immediately on a high phosphate (HP) diet that promotes parathyroid gland hyperplasia, or (2) maintained on a low phosphate (LP) diet that inhibits development of secondary hyperparathyroidism before being switched to the HP diet. Serum chemistries and parathyroid gland (PTG) weights were examined; CaR content and parathyroid cell proliferation (PCNA/Ki-67) were analyzed by immunohistochemistry.
When rats were nephrectomized and placed immediately on a HP diet, parathyroid cell proliferation was significantly increased by day 2 and continued to increase at day 4. CaR content was unchanged at 1 and 2 days post-nephrectomy, but fell by day 4. When nephrectomized rats were maintained for 1 week on a LP diet, then switched to a HP diet, an increase in parathyroid cell proliferation was again seen at day 2; down-regulation of the CaR did not occur until after 7 days of uremia and the HP diet.
These data indicate that parathyroid cell hyperplasia precedes down-regulation of CaR expression in the uremic rat model.
最近有证据表明，钙敏感受体（CaR）的下调与慢性肾衰竭相关的甲状旁腺细胞增生之间存在关联。然而，尚不清楚CaR的下调是先于甲状旁腺细胞增殖并可能引发该增殖，还是CaR表达的降低发生在增生或促进增生的条件之后。本研究探讨了这两个事件的时间关系。
通过次全肾切除术使大鼠发生尿毒症，并将其分为两组：（1）立即给予促进甲状旁腺增生的高磷（HP）饮食；（2）先给予抑制继发性甲状旁腺功能亢进发展的低磷（LP）饮食，之后再改为HP饮食。检测血清生化指标和甲状旁腺（PTG）重量；通过免疫组织化学分析CaR含量和甲状旁腺细胞增殖（PCNA/Ki-67）情况。
当大鼠进行肾切除并立即给予HP饮食时，甲状旁腺细胞增殖在第2天显著增加，并在第4天持续增加。肾切除术后1天和2天CaR含量未发生变化，但在第4天下降。当肾切除大鼠先给予LP饮食1周，然后改为HP饮食时，在第2天再次观察到甲状旁腺细胞增殖增加；直到尿毒症和HP饮食7天后才出现CaR下调。
这些数据表明，在尿毒症大鼠模型中，甲状旁腺细胞增生先于CaR表达下调。
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