妊娠期高碘对子代大鼠甲状腺功能和大脑皮质超微结构的影响
Influence of high iodine during gestation on thyroid function and cerebral cortical ultrastructure in offspring rats
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摘要:目的 建立妊娠期碘过量模型, 观察过量碘对子代大鼠甲状腺功能和大脑皮质形态学的改变, 探讨妊娠期碘过量对子代大鼠甲状腺和大脑发育的影响。方法 选取断乳两周的SPF级雌性Wistar大鼠90只, 随机分成适碘对照(normal iodine, NI)组、轻度碘过量(mild iodine excess, MIE)组和严重碘过量(severe iodine excess, SIE)组, 每组30只, 每组动物均给予低碘动物饲料, 通过饮用含不同浓度碘化钾(KI)的去离子水建立不同碘摄入模型, 碘酸钾浓度分别为183、2 283和11 617 μg/L, 干预3个月后交配受孕。子代大鼠于21天腹主动脉取血, 检测游离三碘甲状腺原氨酸(free triiodothyronine, FT3)、游离甲状腺素(free thyroxine, FT4)和促甲状腺素(thyrotropin, TSH)激素水平, 同时每组各取7只子代大鼠的大脑皮质采用透射电镜观察神经元超微结构。结果 SIE组、MIE组母鼠尿碘水平分别为2 368.7和644.2 μg/L, 均显著高于NI组286.8 μg/L(P < 0.05);SIE组子代大鼠血清FT3水平与NI组比较, 差异具有统计学意义(P < 0.05);SIE组、MIE组子代大鼠血清FT4和TSH水平与NI组比较, 差异均具有统计学意义(P < 0.05)。透射电镜结果显示, MIE组和SIE组子代大鼠大脑皮质神经元内部均出现不同程度损伤, 可见神经细胞核肿胀、扩张, 部分线粒体重度水解、出现空泡样变, 粗面内质网囊腔肿胀, 有髓神经髓鞘分层, 突触小泡节段不完整、变窄、轴突出现水肿等病理性改变。结论 过量碘摄入可影响子代大鼠甲状腺功能, 且妊娠期轻度碘过量和严重碘过量均可对子代大鼠大脑皮质造成病理性损伤, 进而影响子代脑发育及功能。Abstract:Objective To establish a model of gestational iodine overdose to observe the changes in thyroid function and cerebral cortical morphology in offspring rats, and to explore the influence of iodine overdose during gestation on thyroid and brain development in offspring rats.Methods A total of 90 specific pathogen-free female Wistar rats weaned for two weeks were selected and randomly divided into normal iodine (NI) group, mild iodine excess (MIE) group, and severe iodine excess (SIE) group according to body weight, with 30 rats in each group. All rats were fed with a low-iodine diet, and different iodine intake models were established by drinking deionized water containing different concentrations of potassium iodide (KI) (183, 2 283, and 11 617 μg/L, respectively). After 3 months of intervention, the rats were mated and conceived. Blood samples were collected from the abdominal aorta of the offspring rats on day 21 to measure the levels of free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH). Meanwhile, the cerebral cortex was collected from 7 offspring rats of each group to observe neuronal ultrastructure by transmission electron microscopy.Results The levels of urinary iodine in SIE and MIE groups were 2 368.7 and 644.2 μg/L, respectively, which were significantly higher than that in NI group (286.8 μg/L) (P < 0.05). There was a significant difference in the serum level of FT3 between the offspring rats of SIE group and the NI group (P < 0.05), and there were significant differences in the serum levels of FT4 and TSH between the offspring rats of SIE/MIE groups and the NI group (P < 0.05). The result of transmission electron microscopy showed that both the MIE group and the SIE group offspring rats had varying degrees of damage in cerebral cortical neurons. There were pathological changes including swelling and expansion of neuronal nuclei, severe hydrolysis and vacuolation of the mitochondria, swelling of the rough endoplasmic reticulum vesicles, delamination of the myelin sheath of myelinated nerve, incomplete and narrowed synaptic vesicle segments, and edema of axons.Conclusion Excessive iodine intake can affect the thyroid function of offspring rats, and both mild and severe iodine overdose during gestation can cause pathological damage to the cerebral cortex of offspring rats, which in turn affects the brain development and function of the offspring.
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