摘要目的 观察长期氟过量对大鼠甲状腺过氧化物酶(TPO)活性、TPO mRNA表达的影响,并探讨其可能的机制.方法 选用雄性SD大鼠40只,按体质量分为对照组、低氟组、中氟组、高氟组,每组10只,分别饮用含氟化钠0.40(普通自来水)、15.00、30.00和60.00 mg/L的自来水,均食用普通粮食配制的饲料.喂养180 d后处死.测定血清FT3和FT4;采用改良愈创木酚法测定甲状腺TPO活性;半定量RT-PCR方法检测甲状腺TPO mRNA表达水平.结果 低、中、高氟组血清FL3水平[(3.62±0.47)、(3.57±0.55)和(3.30±0.68)pmol/L]与对照组[(3.64±0.45)pmol/L]相比虽呈下降趋势,但差异无统计学意义(P＞0.05)；高氟组血清FT4水平[(8.64±1.72)pmol/L]低于对照组、低、中氟组[(13.08±1.69)、(12.68±1.32)、(12.05±1.43)pmol/L,P均＜0.05].对照组、低氟组、中氟组、高氟组甲状腺细胞TPO活性[(1.572±0.064)、(1.414±0.086)、(1.322±0.049)、0.960±0.083)U/L]随着氟浓度的升高而明显降低,任意两组组间比较差异均有统计学意义(P均＜ 0.05),TPO活性与氟浓度呈显著负相关(r=-0.955,P＜0.05).半定量RT-PCR结果显示:对照组、低氟组、中氟组、高氟组甲状腺TPO mRNA表达水平(0.936±0.160、0.368±0.095、0.115±0.018、0.016±0.008)随着氟浓度升高而明显降低,任意两组组间比较差异均有统计学意义(P均＜0.05).结论 长期摄入过量氟抑制甲状腺TPO活性和TPO的表达,影响甲状腺激素合成.

abstractsObjective To study the effect of long-term fluoride excess on the activity of thyroid peroxidase (TPO) and the expression of TPO mRNA in rat thyroid,and explore the underlying mechanism.Methods Forty male SD rats were randomly divided into four groups based on their body mass(n =10 in each group):control group,low-fluoride group,moderate-fluoride group and high-fluoride group,and rats were fed on water containing 0.40(tap water),15.00,30.00 and 60.00 mg/L NaF,respectively,eating ordinary food formulated feed.All rats were sacrificed 180 days afterwards.Serum FT3 and FT4,TPO activity and mRNA expression level were determined by radio-immunoassay,modificd guaiacol method and semi-quantitative RT-PCR,respectively.Results Although serum FT3 levels in low-fluoride [(3.62 ± 0.47)pmol/L],moderate-fluoride [(3.57 ± 0.55)pmoi/L]and high-fluoride [(3.30 ± 0.68)pmol/L]treated groups were decreased compared with the control[(3.64 ± 0.45)pmol/L],the difference was not statistically significant (P ＞ 0.05).Serum T4 levels of the high-fluoride group [(8.64 ± 1.72)pmol/L]were significantly lower compared with other groups[(13.08 ± 1.69),(12.68 ± 1.32),(12.05 ± 1.43)pmol/L,all P ＜ 0.05].TPO activity in control,low-fluoride,moderate-fluoride and high-fluoride-treated groups[(1.572 ± 0.064),(1.414 ± 0.086),(1.322 ± 0.049),(0.960 ± 0.083)U/L]was decreased with the dose of fluoride increasing,the difference was statistically significant between any two groups(all P ＜ 0.05).The TPO activity was negatively correlated with the dose of fluoride(r =-0.955,P ＜ 0.05).With increased fluoride,the expression of TPO mRNA (0.936 ± 0.160,0.368 ± 0.095,0.115 ± 0.018,0.016 ± 0.008) decreased,the difference was statistically significant between any two groups (all P ＜ 0.05).Conclusion Chronic fluoride excess inhibits the activity and the expression of TPO as well as thyroid hormone synthesis.