肾性甲状旁腺功能亢进患者甲状旁腺素钙敏感受体的表达

Depressed expression of calcium sensing receptor in parathyroid glands of uremic hyperparathyroidism

目的 研究肾性甲状旁腺功能亢进（甲旁亢）患者甲状旁腺组织钙敏感受体（ＣａＲ）的表达，探讨ＣａＲ在肾性甲旁亢发病机制中的作用。方法用免疫组织化学的方法，比较正常对照组和继发性甲旁亢（ＳＨＰＴ）组甲状旁腺ＣａＲ蛋白质的表达。结果ＣａＲ在正常甲状旁腺组织的细胞膜和细胞浆均有表达，细胞阳性率为（７５．２０±２．３１）％，而ＳＨＰＴ组为（２７． ８８ ± ４． ９０）％，明显减少（Ｐ＜０．０１）。弥漫性增生和结节性增生之间差异也有显著性［分别为（４０ ．００ ±３． ３４）％和 （１５． ７５±１．７５）％，Ｐ＜０． ０１］。ＣａＲ表达阳性率与腺体重量呈负相关（ｒ＝－０．８６，Ｐ＜０．０１）。结论严重肾性甲旁亢患者甲状旁腺ＣａＲ表达明显下降，结节性增生比弥漫性增生下降更显著，是引起ＰＴＨ过度分泌的重要原因。上调ＣａＲ的表达或激活ＣａＲ的功能将成为肾胜甲旁亢新的治疗目标。

Objective TO study the expression of calcium sensing receptor (CaR) protein in parathyroid tissue of uremic secondary hyperparathyroidism (SHPT). Methods The expressions of CaR in normal controls(n = 5) and parathyroid glands, including five diffuse hyperplasia and five nodular hyperplasia obtained from uremic hyperparathyroidism patients(n = 5) were examined by immunohistochemistry. Results The CaR protein expressed both in the cellular membrane and cytoplasm in normal parathyroid tissue. The CaR expression was significantly decreased in SHPT compared to that in normal controls [ (27. 88 ±4. 90)% vs(75. 20 ± 2. 31 )%, P < 0. 01 ]. The positive cell rate was lower in nodular hyperplasia than that in diffuse hyperplasia[ (15. 75 ± 1. 75) % vs. (40 ± 3. 34) %, P < 0.01]. In diffuse hypemlasia, the immunostaining of cytoplasm diminished markedly whereas the membrane staining was still obvious in some cells. In nodular hyperplasia, the CaR expression was decreased in both cytoplasm and membrane. There was a negative correlation between the expression of CaR and the weight of gland(r = - 0. 86, P < 0. 01). Conclusion The CaR expression in parathyroid glands of uremic hyperparathyyroidism is decreased, especially in nodular hyperplastic tissue. Decreased CaR expression would be compatible with a less efficient control of PTH secretion. The parathyroid calcium receptor will be a novel therapeutic target for treating uremic hyperparathyroidism.