Parathyroid hyperplasia in uremic rats precedes down-regulation of the calcium receptor
Parathyroid hyperplasia in uremic rats precedes down-regulation of the calcium receptor
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DOI：
10.1046/j.1523-1755.2001.00027.x
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发表时间：
2001-11-01
影响因子：
19.6
通讯作者：
Brown, AJ
中科院分区：
文献类型：
--
作者：
Ritter, CS;Finch, JL;Brown, AJ
背景最近的证据表明，钙敏感受体（CaR）的下调和甲状旁腺细胞增生之间的关系，与慢性肾功能衰竭。它是不知道的，但是，如果下调钙调素受体之前，也许启动，甲状旁腺细胞增殖，或者如果减少钙调素受体的表达发生后增生或条件促进it. The目前的研究检查这两个事件的时间关系。通过肾次全切除术使大鼠患尿毒症，并（1）立即给予促进甲状旁腺增生的高磷酸盐（HP）饮食，或（2）维持低磷酸盐（LP）饮食，以抑制继发性甲状旁腺功能亢进的发展，然后转为HP饮食。检测血清生化指标、甲状旁腺（PTG）重量、钙调素受体（CaR）含量及甲状旁腺细胞增殖（PCNA/Ki-67）。当大鼠肾切除后立即给予HP饮食时，甲状旁腺细胞增殖在第2天显著增加，并在第4天继续增加。CaR含量在肾切除术后1天和2天不变，但在第4天下降。当肾切除大鼠维持1周的LP饮食，然后切换到HP饮食，甲状旁腺细胞增殖的增加再次看到在第2天;下调的CaR没有发生，直到7天的尿毒症和HP饮食。这些数据表明，甲状旁腺细胞增生之前，在尿毒症大鼠模型中的CaR表达下调。
Background. 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.Methods. 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.Results. 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; downregulation of the CaR did not occur until after 7 days of uremia and the HP diet.Conclusion. These data indicate that parathyroid cell hyperplasia precedes down-regulation of CaR expression in the uremia rat model.