Klotho蛋白在甲状旁腺细胞弥漫性增生与结节性增生中的不同表达探讨

Difference expression of Klotho in parathyroid cells with nodular hyperplasia and diffusible hyperplasia

目的探讨Klotho蛋白在慢性肾衰竭继发性甲状旁腺功能亢进症(secondary hyperparathyroidism,SHPT)甲状旁腺细胞不同增生类型中表达的意义。方法选取在武警总医院肾内科住院行甲状旁腺全切术的SHPT患者50例为SHPT组,尸体甲状旁腺组织供体8例为健康对照组,收集其血清及甲状旁腺组织标本,SHPT组甲状旁腺组织按病理表现分为结节性增生组和弥漫性增生组,检测血成纤维细胞生长因子-23(fibroblast growth factor-23,FGF-23)及甲状旁腺激素(parathyroid hormone,PTH)水平,免疫组化检测甲状旁腺组织中Klotho蛋白及增殖指标Ki67的表达。结果①SHPT患者血FGF-23[(1316.80±375.15)pg/ml]与PTH[(2106.00±806.78)pg/ml]呈正相关(r=0.438,P=0.001)。②SHPT患者血FGF-23与甲状旁腺组织中Klotho的表达呈负相关(r=-0.379,P=0.007),血PTH与Klotho蛋白呈负相关(r=-0.361,P=0.01)。③SHPT组甲状旁腺细胞中Ki67的表达显著高于对照组(F=54.417,P=0.000),Klotho蛋白的表达显著低于对照组(F=49.243,P=0.000);SHPT组结节性增生甲状旁腺组织中Ki67的表达显著高于弥漫性增生组(t=3.760,P=0.001),Klotho蛋白的表达显著低于弥漫性增生组(t=6.039,P=0.000)。结论结节性增生甲状旁腺组织中Klotho蛋白表达低于弥漫性增生组织可能是导致SHPT患者甲状旁腺呈不同增生方式的重要原因。

Objective To investigate the different expression of Klotho protein in parathyroid cells with nodular hyperplasia and with diffusible hyperplasia from secondary hyperparathyroidism （SHPT） patients.Method A total of 50 SHPT patients with parathyroidectomy were recruited as the SHPT group,and parathyroid tissues from 8 cadavers were used as the healthy control group.SHPT patients were subdivided into diffusible hyperplasia subgroup and nodular hyperplasia subgroup according to their pathology changes.Serum fibroblast growth factor-23 （FGF-23） and parathyroid hormone （PTH） were assayed in SHPT patients.Klotho and Ki67 expressions in parathyroid tissues were examined by immunohistochemistry method.Results ① Serum FGF-23 was positively correlated with PTH （r=0.438,P=0.001） in SHPT patients; ② serum FGF-23 and serum PTH were negatively correlated with the expression of Klotho protein in parathyroid cells （r=-0.379,P=0.007 for serum FGF-23; r=-0.361,P=0.01 for Klotho）; ③ in the SHPT group,the expression of Ki67 increased significantly （F=54.417,P=0.000） and the expression of Klotho decreased significantly （F=49.243,P=0.000）,as compared with those in the healthy control group.In nodular hyperplasia subgroup,the expression of Ki67 increased significantly （t=3.760,P=0.001） and the expression of Klotho decreased significantly （t=6.039,P=0.000）,as compared with those in diffusible hyperplasia subgroup.Conclusion Klotho protein may contribute to the different types of parathyroid cell hyperplasia in SHPT patients.