不同孕期补充甲状腺激素对子鼠脑组织生长相关蛋白-43表达的影响

Effects of thyroid hormone supplement in different stages of gestation on the expression of growth-associated protein-43 in the brain tissue of rat offspring

目的研究不同孕期低碘孕鼠补充甲状腺激素对子鼠脑组织生长相关蛋白（GAP）-43表达的影响，探讨甲状腺激素不足造成的脑发育落后现象的可能机制。方法1月龄Wistar大鼠160只，雌、雄各半。雌性大鼠随机分为8组：正常组和7个低碘组，每组10只。各组均饲以低碘饲料，正常组饮用碘浓度为200ug／L的碘酸钾溶液，总碘摄入量相当于大鼠生理碘需要量，低碘组饮用去离子水。3个月后，与正常Wistar雄鼠进行交配。选择1个低碘组不补充甲状腺激素作为阴性对照，其余6组分别在妊娠早期（孕1～17d）和妊娠中、晚期（孕18d-出生后20d）补充高、中、低剂量甲状腺激素，剂量分别为：3．5、2、0．5ug／100g体重。8组分别取新生当天、生后7d、14d、21d、28d的子鼠脑组织，应用SABC法检测GAP-43在神经细胞中的表达，图像分析方法定量检测蛋白的含量。结果低碘组不同日龄子鼠脑组织GAP-43的表达普遍低于同日龄正常组（P〈0．05），只有在28d时大于正常组（P〈0．05）；对低碘孕鼠给予中、高剂量的甲状腺激素，可以使子鼠脑组织GAP-43的表达接近正常水平，尤其是在孕早期补充甲状腺激素（P〈0．05）。结论孕鼠低碘导致子鼠脑组织GAP-43表达降低，低碘孕鼠补充中剂量以上的甲状腺激素，可以使子代GAP-43的表达水平接近正常，在孕早期补充效果更好。

Objects To observe the effects of thyroid hormone supplement in different stages of gestation of low-iodine pregnant rats on expression of growth-associated protein（GAP）-43 in the brain tissue of rat offspring, and explore the possible mechanism of brain development defect caused by thyroid hormone deficiency. Methods There are 160 one-month-old Wistar rats,50% male and 50% female. The female rats were randomly divided into eight groups including normal group and 7 low iodine groups, 10 rats per group. Rats were fed with low iodine feed. Normal group were given 200 ug/L KIO3. The total iodine intake is equivalent to rat physiological iodine requirements. Other groups drunk deionized water. After 3 months, female rats were mated with normal male rats. Rats of one low iodine group as negative controls are not supplied with thyroid hormone. The other six groups are differently supplied with high/medium/low doses of thyroid hormone in early gestation （pregnant lst-17th day） groups and late gestation （pregnant 18th day-20th day after birth） groups. High/medium/low doses of thyroid hormone is respectively 3.5,2,0.5 ug/100 g weight. Brain tissues of new-born,7-day,14-day,21-day,28-day offspring in every group were taken for sampies. The expression of GAP-43 of every group was detected by immunohistochemistry （SABC） and analysed by image method. Results The expression of GAP-43 of neonatal offspring in low iodine group at different time was lower than that in normal group（P 〈 0.05）, only in postnatal 28 d group, GAP-43 expression level is higher（ P 〈 0.05 ）. If low iodine pregnant rats continue to be given the medium or high dose of thyroid hormone,the expression of GAP-43 in offspring can reach the normal, especially in the early gestation. Conclusion Pregnant rats at low iodine state will result in the lower expression of GAP-43 in the brain of neonatal offspring. When more than medium dose of thyroid hormone was supplied in low-iodine pregnant rats,the expression of GAP-43 in the brain of neonatal offspring could be close to normal level,especially in early gestation.