FGF-23通路下调在尿毒症继发性甲旁亢发病机制中的作用

Effect of down-regulation in fibroblast growth factor-23 signaling pathway for secondary hyperparathyroidism by uremic

【目的】探讨成纤维细胞生长因子-23(fibroblast growth factor-23,FGF-23)调节甲状旁腺激素(parathyroid hormone,PTH)信号通路下调是否参与在尿毒症继发性甲旁亢(SHPT)的发生。【方法】选取在我院肾内科住院行甲状旁腺全切术的SHPT患者50例为SHPT组,尸体甲状旁腺供体8例为对照组,检测血PTH及FGF-23水平,免疫组化测定FGFR1、Klotho、Ki67、ERK1/2、p-ERK1/2、Egr-1的表达。【结果】(1)SHPT组患者血FGF-23与PTH呈正比(r=0.438,P=0.001);(2)与对照组相比,SHPT组甲状旁腺细胞FGFR1(P=0.000)、Klotho(P=0.000)、p-ERK1/2(P=0.001)、Egr-1(P=0.000)的表达显著低于对照组,Ki67(P=0.000)的表达显著高于对照组,ERK1/2(P=0.091)在SHPT组及对照组中的表达差异无统计学意义;(3)与弥漫性增生组相比,结节性增生组FGFR1(P=0.001)、Klotho(P=0.000)、p-ERK1/2(P=0.013)、Egr-1(P=0.036)的表达显著低于弥漫性增生组,Ki67的表达显著高于弥漫性增生组(P=0.001),ERK1/2在结节性增生组与弥漫性增生组中的表达无统计学差异;(4)SHPT组患者血PTH与甲状旁腺细胞中FGFR1(r=-0.728,P=0.000)、Klotho(r=-0.361,P=0.010)、ERK1/2(r=-0.656,P=0.000)、p-ERK1/2(r=-0.696,P=0.000)、Egr-1(r=-0.439,P=0.001)的表达均呈负相关,与Ki67的表达呈正相关(r=0.695,P=0.000)。【结论】FGF-23调节PTH通路的下调可能参与尿毒症SHPT患者高PTH的分泌过程,在SHPT的发病机制中发挥一定作用。

[Objective ]To investigate the role of fibroblast growth factor-23（FGF-23） of parathyroid hormone（PTH） in the pathogenesis of uremic secondary hyperparathyroidism（SHPT）. [Method] A total of 50 SHPT patients and 8 cadaver were selected to parathyroidectomy. Serum PTH and FGF-23 were detected. The expression of FGFR1, Klotho, Ki67, ERK1/2, p-ERK1/2 and Egr-1 in parathyroid cells were detected by immunohistochemistry. [Results] （1）In SHPT group, serum FGF-23 was positively correlated with PTH（r = 0.438, P = 0.001）. （2）Compared with control group, the expression of FGFRI（P = 0.000）, Klotho（P = 0.000）,p-ERK1/2（P = 0.001）, Egr-1 （P = 0.000）in SHPT group were significantly decreased, the expression of Ki67（P = 0.000） was significantly increased, the expression of ERK1/2（P = 0.091） had no difference. （3）Compared with diffusible hyperplasia group, the expression of FGFRI（P = 0.001）, Klotho（P = 0.000）, p-ERK1/2（P = 0.013）,Egr-I（P = 0.036）were significantly decreased, the expression of Ki67（P = 0.001）was significantly increased, the expression of ERK1/2 had no difference. （4）In SHPT group, serum PTH was negatively correlated with FGFRI（r = -0.728, P = 0.000）, Klotho（r = -0.361, P = 0.010） ,ERK1/2（r = -0.656,P = 0.000） ,p-ERK1/2（r = -0.696, P = 0.000） ,Egr-1 （r = -0.439, P = 0.001）, and positively correlated with Ki67（r = 0.695, P = 0.000）. [Conclusion] The down-regulation of FGF-23 signal pathway may play a role in the pathogenesis of Uremic secondary hyperparathyroidism.