Vitamin D receptor and PCNA expression in severe parathyroid hyperplasia of uremic patients

摘要

目的研究维生素D受体(VDR)在继发性甲旁亢(SHPT)患者甲状旁腺(PT)中的表达，探讨严重继发性甲旁亢患者对钙三醇抵抗的机制以及与PT增生的关系。 方法7例严重SHPT病人的PT19枚，正常人6枚，用免疫组化ABC法检测细胞增殖核抗原(PCNA)、维生 素D受体表达，计算阳性细胞率。 结果SHPT组PT总重比正常人增加16.1倍，PCNA表达明显增加，分别为(6.35±3.36)‰和(1.73± 1.31)‰(P＜0.001)。结节性增生区(NH)增加更为显著(P＜0.001)，PCNA表达与腺体重量呈正相关(r= 0.58，P＜0.01)。SHPT组VDR阳性率(40.28±13.13)％比对照组(83.79±3.77)％明显减少(P＜0.001)。 结节性较弥漫性增生减少更显著，为(27.14±4.12)％和(49.84±7.33)％(P＜0.001)。VDR表达与腺体 重量、PCNA阳性率均呈负相关(r=-0.46，P＜0.05与r=-0.75，P＜0.001)。 结论SHPT甲旁腺VDR表达明显减少，结节性较弥漫性增生更甚，与PCNA阳性率呈负相关。提示严重 SHPT患者PT细胞VDR明显减少可能是导致对钙三醇抵抗的重要原因，且与细胞增殖有关。%Objective To clarify the role of vitamin D receptor (VDR)expression in parathyroid proliferation and resistance of parathyroid glands to 1,25(OH)2D3 with secondary hyperparathyroidism (SHPT). Methods This study used archive parathyroid with 7 uremic patients. The expression of proliferation cell nuclear antigen (PCNA) and VDR was evaluated in nineteen-surgically excised parathyroid tissues, including 11 diffuse hyperplasia (DH-type) and 8 nodular hyperplasia (NH-type) of parathyroid glands, by immunohistochemistry (avidin-biotin complex method). Results The weight of parathyroid in SHPT was remarkably increased by 16.1 times. The numbers of parathyroid cells were increased by 1.86 times. The rate of PCNA was remarkably increased in parathyroid hyperplasia with SHPT compared with that in control group [(6.35±3.36)‰ vs (1.73±1.31)‰, P<0.001]. The number of PCNA in DH-type was lower than that in NH-type (P<0.001). The density of VDR in the parathyroid with SHPT was significantly decreased [(40.28±13.13)% vs (83.79±3.77)%, P<0.001], VDR immunoreactivity expression in NH-type was lower than that in DH-type [(27.14±4.12)% vs (49.84±7.33)%, P<0.001]. A significantly negative correlation was found between VDR density and the weight of the parathyroid (r=-0.46, P<0.05), the same as VDR and PCNA (r=-0.75, P<0.001). Conclusion VDR density was significantly decreased in parathyroid tissue of uremic patients showing nodular hyperplasia compared with that in diffuse hyperplasia and there was significantly negative correlation between VDR density and the weight of the parathyroid, and this may contribute to the progression of SHPT. Furthermore, VDR deficiency may cause the resistance of parathyroid cells to 1, 25(OH)2D3, in part.