高磷通过局部环氧化酶2途径刺激尿毒症患者甲状旁腺细胞增生

目的 探讨尿毒症时高磷是否通过局部环氧化酶2( COX2)途径刺激人甲状旁腺细胞增生和功能亢进.方法 收集19例行甲状旁腺切除术的尿毒症患者甲状旁腺组织,通过免疫组化和免疫共染法观察COX2和增殖细胞核抗原(PCNA)的表达和分布.进行人甲状旁腺细胞原代培养,分别予高磷和正常磷干预,48 h后检测两组细胞上清液甲状旁腺激素(iPTH)水平；应用Western印迹和实时PCR方法观察细胞中COX2及PCNA的表达.结果 在获取的62枚尿毒症甲状旁腺结节中43枚为结节性增生,19枚为弥漫性增生,均观察到大量PCNA阳性细胞和COX2高表达.在弥漫性和结节性增生的甲状旁腺组织中,分别有80.60％及85.20％的COX2阳性细胞同时表达PCNA.在体外原代培养的尿毒症患者甲状旁腺细胞中,高磷能显著增加iPTH分泌,同时显著上调COX2及PCNA蛋白和基因表达.结论 高磷可能通过局部COX2表达和代谢途径参与尿毒症甲状旁腺细胞增生和功能亢进.

Hyperplasia of parathyroid cells induced by high phosphate via local cyclooxygenase 2 pathway in uremic patients

Objective To explore whether the stimulation effect of high phosphate on hyperplasia of human parathyroid cells and hyperparathyroidism through local cyclooxygenase 2 (COX2) up-regulation pathway. Methods Parathyroid glands were collected from 19 uremic patients undergoing parathyroidectomy. Expressions of COX1, COX2 and proliferative cell nuclear antigen (PCNA) of the glands were detected by immunohistochemistry. Primary parathyroid cells were cultured and treated with high or normal phosphate for 48 hours. Then expressions of COX2 and PCNA were detected by Western blotting and real-time PCR. Results Among 62 glands from above 19 patients, 43 glands were nodular hyperplasia and 19 diffuse hyperplasia. Both high expressions of COX2 and PCNA were found in these blands. Expression of COX2 was found in both oxyphil and chief cells and was more in the diffuse hyperplasia glands than that in the nodular hyperplasia(P<0.05). 80.60% and 85.20% of COX2 positive cells in diffuse hyperplasia glands and nodular hyperplasia also expressed PCNA. High phosphate could stimulate iPTH secretion in vitro(P<0.05). Expressions of COX2 and PCNA were higher in high phosphate group.(P<0.05). Conclusion High phosphate may stimulate the hyperplasia of parathyroid cells by up-regulating the local COX2 expression.