NPS R-467对甲状旁腺细胞分泌甲状旁腺激素的作用

Effect of NPS R-467 on PTH secretion of cultured parathyroid cells from secondary hyperparathyroidism patients

目的 观察钙受体 (CaR)激动剂NPSR 46 7对严重继发性甲状旁腺功能亢进 (SHPT)患者甲状旁腺细胞分泌甲状旁腺激素 (PTH)功能的影响。方法 对严重SHPT患者手术切除的甲状旁腺组织进行细胞培养。在培养 90min时加入NPSR 46 7及其异构体NPSS 46 7,后者作为阴性对照。药物的终浓度分别为 2 5、5 0和 10 0nmol/L ,用放免法检测加药 15、30、6 0min后培养上清液中PTH的分泌量。结果 加药 15min后 ,NPSR 46 7组和阴性对照组PTH的分泌值非常接近 ,约为 1 8ng/10 5细胞。随后NPSS 46 7组PTH的测定值呈上升趋势 ,加药 6 0min后达 2 3ng/10 5细胞 ,而NPSR 46 7组在加药 30min后降为对照组的 80 % ,加药 6 0min后降为对照组的 6 0 % ,不同剂量组间NPSR 46 7的效应无明显差异。结论 CaR激动剂NPSR 46 7能明显抑制重症SHPT患者甲状旁腺细胞PTH的分泌 。

Objective To observe the effect of NPS R 467, a calcimimetic, on PTH secretion of cultured parathyroid cells from severe secondary hyperparathyroidism (SHPT) patient. Methods The parathyroid tissue from a severe SHPT patient (iPTH: 2 000 pg/ml) who had underwent parathyroidectomy was cultured in medium containing 1.05 mmol/L Ca and 0.8 mmol/L Mg. After 90 minutes′ culture, NPS R 467 or NPS S 467, as negative control, with the final concentrations of 25, 50, and 100 nmol/L was added. The supernatant of medium was aspirated after 15, 30, and 60 minutes and iPTH therein was measured by radioimmunoassay. Results There was no difference between the PTH concentrations in NPS R 467 group and NPS S 467 15 minutes after the reagents were added (1.8 ng/10 5 cells). In the NPS S 467 group, the PTH secretion was elevated along with the culture time, at 60 minutes up to 2.3 ng/10 5 cells. The PTH concentration of NPS R 467 was 80% of that of control group 30 minutes later and 60% of that in control group 60 munites later. No difference was found among the effects of NPS R 467 at different concentrations. Conclusion The calcimimetic NPS R 467 significantly suppresses the PTH secretion, even in severe uremic hyperparathyroidisim patient. It is an effective medicine for hyperparathyroidism.