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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200 μg/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1～17 d)和妊娠中、晚期(孕18 d～出生后20 d)补充高、中、低剂量甲状腺激素,剂量分别为:3.5、2、0.5 μg/100 g体重.8组分别取新生当天、生后7d、14 d、21 d、28 d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28 d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 μg/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 μg/100 g weight.Brain tissues of new-born,7-day,14-day,21-day,28-day offspring in every group were taken for samples.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.