Graves病患者血清成纤维生长因子23和Klotho蛋白的表达及其意义

Elevated serum concentrations of FGF23 and Klotho in patients with Graves disease and their significance

目的 探讨成纤维细胞生长因子23（fibroblast growth factor 23,FGF23）,Klotho蛋白与Graves病（Graves disease,GD）之间的关系.方法 选取2016年3月至2016年11月在复旦大学附属金山医院新诊断且未治疗的Graves病患者43例（GD组）,健康体检者27名,收集外周静脉血清,检测血钙、血磷以及GD组的甲状腺功能,采用酶联免疫吸附（ELISA）法检测各组FGF23、Klotho蛋白、1,25-二羟维生素D3的表达水平,比较GD组与与正常对照组之间FGF23、Klotho蛋白、1,25-二羟维生素D3及血钙、血磷的组间差异,并分析各项指标间的相关性,探讨FGF23、Klotho蛋白与GD发病间的关系.结果组间对比结果：（1）甲状腺功能中促甲状腺激素在GD组中显著低于正常组,差异有统计学意义[0.003（0.002,0.004）mU/L与1.650（0.810,2.140）mU/L,Z=-7.587,P〈0.05];GD组中促甲状腺激素受体抗体、游离三碘甲状腺原氨酸、游离甲状腺素显著高于正常组[促甲状腺激素受体抗体：9.63（3.89,21.29）U/L与0.60（0.38,0.97）U/L,游离三碘甲状腺原氨酸：23.36（11.61,38.00 pmol/L与4.63（4.03,4.92）pmol/L],游离甲状腺素：4.34（33.94,100.00）pmol/L与17.69（15.80,20.35）pmol/L;Z值分别为-6.694,-6.878,-6.836,P均〈0.05;（2）甲状腺机能亢进患者血清中FGF23,Klotho,磷表达量显著高于正常组,差异有统计学意义[FGF23：（524.2±66.7）ng/L与（467.2±64.5）ng/L,Klotho：8.29（6.89,11.37）ng/L与6.69（6.36,7.53）ng/L,磷：1.33（1.03,1.52）mmol/L与1.02（0.84,1.20）mmol/L;t=3.517,Z值分别为-3.936,-3.795,P均〈0.05].相关性分析结果显示：（1）FGF23与Klotho、促甲状腺激素受体抗体、游离甲状腺素、1,25-二羟维生素D3、磷、钙a均无相关性（P均〉0.05）;（2）Klotho与促甲状腺激素受体抗体、游离甲状腺素、1,25-二羟维生素D3、磷、钙均无相关性（P均〉0.05）.结论 GD中FGF23表达升高,可能参与GD发病,而Klotho在GD患者中升高,可能是GD患者体内异常免疫状态引起反应性升高,以起到保护性作用.

Objective To investigate the relationship between FGF23 and Klotho in GD patients. Methods From March 2016 to November 2016, forty-three newly diagnosed and untreated Grave disease patients （GD group） and 27 healthy subjects were selected. Meanwhile,Peripheral venous serum was collected to detect serum calcium, phosphorus and thyroid function in GD group. The levels of FGF23, Klotho protein and 1 in each group were detected by enzyme-linked immunosorbent assay （ ELISA ） . The expression levels of FGF23,Klotho protein and 1,25-dihydroxyvitamin D3 were detected by enzyme-linked immunosorbent assay （ ELISA ） . The differences of FGF23, Klotho protein, 1, 25-dihydroxyvitamin D3, serum calcium and phosphorus between GD group and normal control group were compared,and the correlation between each index was analyzed. The relationship between FGF23 and Klotho protein and the pathogenesis of GD was explored. Results （ 1） Thyrotropin in thyroid function was significantly lower in GD group than that in normal group,and the difference was statistically significant （ 0. 003 （ 0. 002, 0. 004 ） mU/L vs. 1. 650 （ 0. 81, 2. 14 ） mU/L, Z=- 7. 587,P〈0. 05] . Thyrotropin receptor antibodies,free triiodothyronine and free thyroxine in GD group were significantly higher than those in normal group. There were [ thyroid stimulating hormone receptor antibodies：9. 03（3. 89,21. 29）） U/L vs. 0. 60（0. 38,0. 97）） U/L,free triiodothyronine：23. 36（11. 61,38. 00）） pmol/L vs. 4. 63（4. 03,4. 92）） pmol/L,free thyroxine：4. 34（33. 94,100. 00） pmol/Lvs. 17. 69（15. 80,20. 35） pmol/L;Z=-6. 694,-6. 878,-6. 836,P〈0. 05];（ 2） The serum levels of FGF23,Klotho and phosphorus in patients with hyperthyroidism were significantly higher than those in the normal group,and the difference was statistically significant [FGF23：（524. 2±66. 7） ng/L vs. （467. 2±64. 5） ng/L,Klotho：8. 29（6. 89,11. 37） pg/ml vs. 6. 69 （6. 36,7. 53） pg/ml,phosphorus：1. 33（1. 03,1. 52） mmol/L vs. 1. 02（0. 84,1. 20） mmol/L; t=3. 517,Z=-3. 936,-3. 795,P〈0. 05]. The Results of correlation analysis showed that： （1） There was no correlation among FGF23 and Klotho,thyroid stimulating hormone receptor antibody,free thyroxine,1,25-dihydroxyvitamin D3,phosphorus and calcium a （ P〉0. 05）;（ 2） There was no correlation among Klotho and thyroid stimulating hormone receptor antibody, free thyroxin, 1, 25-dihydroxyvitamin D3, phosphorus and calcium （ P〉0. 05 ） . Conclusion The elevated expression of FGF23 in GD may be involved in the pathogenesis of GD, and the elevated expression of Klotho in GD may be due to the abnormal immune status in GD patients,which may play a protective role.