碘对人甲状腺细胞凋亡的影响

Effect of iodine on apoptosis in cultured human thyrocytes

目的 研究碘对人甲状腺细胞凋亡的影响 ,探讨其在甲状腺疾病发病机制中的作用和意义。方法 分别以不同浓度NaI刺激单层培养的人正常甲状腺上皮细胞 ,采用流式细胞术、Western印迹和半定量RT PCR等方法分别检测刺激前后细胞凋亡率、凋亡相关蛋白Fas、Bcl 2和Bak以及Fas、可溶性Fas(sFas)mRNA表达的变化 ,并以ELISA法检测细胞培养液中sFas的含量。结果 (1)低浓度NaI(10 -8mol/L)明显抑制细胞凋亡 (P <0 .0 5 ) ,中、高浓度 (10 -6～ 10 -4 mol/L)时显著增加细胞调亡 (P <0 .0 5 ) ;(2 )低浓度NaI显著促进sFas蛋白及mRNA的表达 (P <0 .0 5 ) ,不影响Fas蛋白及mRNA的表达 ;(3)中、高浓度NaI则明显增加Fas蛋白及mRNA表达 ,但抑制sFas蛋白及mRNA表达 (P <0 .0 5 ) ;(4 )在 10 -8～ 10 -4 mol/L浓度范围内 ,NaI剂量依赖性地抑制甲状腺上皮细胞表达Bcl 2蛋白 ,但显著增加Bak蛋白的表达 (P <0 .0 5 )。结论 碘可通过调节Fas、sFas、Bcl 2及Bak的表达 ,影响甲状腺细胞凋亡的发生 ,其中低浓度碘可抑制凋亡 ,而中、高浓度碘则促进细胞凋亡。

Objective To investigate the influence of iodine on apoptosis of thyrocytes and to study the effect of iodine on the pathogenesis of thyroid diseases. Methods Normal human thyrocytes were cultured in the absence or presence of 10 -8 ～10 -4 mol/L NaI. Apoptosis, Fas expression, Bcl-2 and Bak expression and Fas and soluble Fas (sFas) mRNA levels in thyrocytes were detected by flowcytometry, Western blot and semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) respectively, sFas was detected in supernatant of cultured thyrocytes by ELISA. Results (1) Low concentration of iodine (10 -8 mol/L) could inhibit apoptosis, while high concentrations of iodine (10 -6 ～10 -4 mol/L) increased apoptosis (P<0.05). (2)sFas expression and sFas mRNA level in thyrocytes were markedly increased by low concentration of iodine (P<0.05), while Fas expression and Fas mRNA level were not influenced by low concentration of iodine. (3) High concentrations of iodine significantly increased Fas expression and Fas mRNA level, but inhibitedsFasexpressionandsFasmRNAlevelinthyrocytes (P<0.05). (4) Iodine of 10 -8 ～10 -4 mol/L decreased the Bcl-2 expression in a does-dependent manner, but increased the expression of Bak in thyrocytes. Conclusion Apoptosis is influenced by iodine in cultured normal human thyrocytes through the modulation of Fas, sFas, Bcl-2 and Bak expression. Low concentration of iodine inhibits apoptosis, whereas high concentrations of iodine increase the rate of apoptosis.