目的:研究 Graves 病患者细针穿刺组织中 EGFR、Ku70、NF-κB 和 Bcl-2基因的表达水平,探讨其在 Graves 病发生发展中的作用。方法Graves 病组患者59例,平均年龄(44.66+12.94)岁,其中男16例,女43例;甲状腺结节周围正常甲状腺组织标本27例为对照组,平均年龄(44.64+14.27)岁,其中男6例,女21例。采用实时荧光定量逆转录-多聚酶链反应(RT-PCR)法检测 EGFR、Ku70、NF-κB 和 Bcl-2在 Graves 病及对照组甲状腺组织中的表达,t 检验分析基因表达水平差异;Pearson 相关法分析基因表达与临床特征及相关血清学指标之间的关系。结果上述基因在对照组及 Graves 病甲状腺组织中都有不同程度的表达。Graves 病患者组织中 EGFR 及 Ku70的表达水平明显高于对照组甲状腺组织(1.752±0.660 vs .0.859±0.125,P <0.05;3.304±0.402 vs .0.768±0.102,P <0.001);NF-κB 及 Bcl-2的表达水平明显低于对照组甲状腺组织(0.578±0.066 vs .0.884±0.085,P <0.001;0.834±0.086 vs .1.235±0.261,P <0.05)。Graves 病组织中 NF-κB 与 Bcl-2表达水平呈正相关(r =0.399,P <0.001)。Graves 病组织中 Ku70的表达水平与血清 TgAb 水平呈正相关(r=0.263,P<0.05),而其他基因表达与相关血清学指标无关(P 均>0.05)。结论Ku70、EGFR、NF-κB、Bcl-2介导的信号转导通路可能参与了 Graves 病的发生、发展过程。
Objective To investigate the roles of Ku70,epidermal growth factor receptor (EGFR),nuclear factor-kappa B (NF-κB)and Bcl-2 genes in the pathogenesis of Graves’disease.Methods Fine needle biopsies of 59 patients [M:F 1 6:43;mean age (44.66 ± 12.94)y)]diagnosed as having Graves’disease and 27 [M:F 6:21;mean age (44.64± 14.27)y]control normal tissues were collected.The mRNA expressions of EGFR,Ku70,NF-κB,and Bcl-2 were detected by Real-time polymerase chain reaction (RT-PCR).The Student’s t test was performed to analyze differences between patients with Graves’disease and control subjects.Pearson correlation analysis was applied to detect the relationship between gene mRNA expression and serological indexes.Results Compared with those of control subjects,the mRNA expression levels of EGFR (0.859 ±0.125 vs .1.752 ±0.660,P 〈0.05)and Ku70 (0.768±0.102 vs .3.304±0.402,P 〈0.001)were significantly higher in Graves’disease patients.However, the mRNA expressions of Bcl-2 (1.235±0.261 vs .0.834±0.086,P 〈0.05)and NF-κB (0.578±0.066 vs .0.884 ±0.085,P 〈0.05)were much lower in Graves’disease patients.Furthermore,the mRNA expression of Bcl-2 was positively correlated with that of NF-κB (r =0.399,P 〈0.05 ).The Pearson correlation analysis showed that the higher expression of Ku70 was positively associated with the serum TgAb level (r = 0.263,P 〈0.05 ),but expressions of the other target genes were not significantly related to the serological indexes (all P 〉0.05 ). Conclusion The signal transduction pathways mediated by Ku70,EGFR,NF-κB and Bcl-2 may participate in the occurrence and development of Graves’disease.