硒及GPX-3、SePP基因敲除对小鼠甲状腺形态及功能的影响

EFFECT OF SELENIUM AND GPX-3, SePP GENE KNOCKOUT ON THYROID MORPHOLOGY AND FUNCTION IN MICE

目的研究不同硒摄入水平及SePP、GPX-3基因敲除对小鼠甲状腺形态及功能的影响,并探讨甲状腺组织的硒供给机制。方法野生型雄性C57BL/6小鼠,随机分缺硒(n=11)、适硒(n=5)和富硒(n=5)3组。选择C57BL/6基因敲除小鼠,分为GPX-3基因敲除组(n=11)及SePP基因敲除组(n=10),分别饲以适硒及富硒饲料。实验干预20w后,杀死动物,取材检测。观察各组小鼠甲状腺组织病理改变并检测各组小鼠甲状腺激素水平。结果与适硒组比较,各组甲状腺组织均有不同程度的增殖。与适硒组比较,缺硒组总三碘甲状腺原氨酸(TT3)、总甲状腺素(TT4)及总促甲状腺激素(TSH)均无明显变化(P>0.05);富硒组TT4水平明显低于缺硒组及适硒组(P<0.05),TT3比较虽无统计学差异,但激素水平明显下降;与适硒组比较,GPX-3基因敲除组血清TT3、TT4、TSH水平均未见明显变化;与富硒组比较,SePP基因敲除组血清TT3、TT4、TSH水平均未见明显变化。结论甲状腺在机体硒缺乏时能优先地获得硒。甲状腺组织在缺乏SePP或GPX-3时,甲状腺功能仍可维持在正常水平。甲状腺组织中的硒可能存在其他转运供给机制。

Objective To study the effect of selenium（Se） level, selenoprotein P（SePP） and glutathione peroxidase 3（GPX-3） gene knockout on thyroid morphology and function in mice, and explore the role of SePP, GPX-3 in Se transportation. Methods Wild-type C57BL/6 mice were randomly divided into 3 groups： Se-deficient group（n=11）, Se-adequate group（n=5）, Se-abundant group（n=5）. The mice selected for gene knockout were divided into GPX-3 gene knockout group（n=11） and SePP knockout group（n=10）, and were fed Se-adequate and Se-abundant feed, respectively. Twenty weeks later, all animals were killed. The pathological changes in thyroid tissue were checked and the thyroid hormone levels were measured. Results Compared to Se-adequate group, the thyroids in each group were hyperplasied distinctly. Compared to Se-adequate group, the concentrations of total triiodothyronine（TT3）, total thyroxine（TT4） and thyroid stimulating hormone（TSH） in Se-deficiency group were not changed significantly（P 0.05）; the concentration of TT4 in Se-abundant group was significantly lower than that in Se-deficiency and adequate groups（P〈0.05）, and the level of TT3 was also decreased, though there was no significant difference. Compared to Se-adequate group, TT3, TT4, TSH in GPx-3 gene knockout group were not changed significantly. Compared to Se-abundant group, the levels of total TT3, TT4, TSH in SePP gene knockout group was not changed significantly. Conclusion Long-term excessive intake of Se can induce hypothyroidism. Thyroid function can be maintained normally in the absence of SePP or GPX-3. Se enters thyroid tissue via a variety of transport systems.