妊娠早期左旋甲状腺素治疗亚临床甲减母鼠可改善仔鼠神经智力发育  

Treatment with levothyroxine in early maternal subclinical hypothyroidism may improve the neural development of the progeny

作　　者：鲁丽[2] 于晓会[1] 滕卫平[1] 单忠艳[1] 刘迪杰[1] 王森[1] 高芸[1] 毛金媛[1] 范晨玲[1] 王红[1] 张红梅[1] 

机构地区：[1]中国医科大学附属第一医院内分泌科,内分泌研究所,沈阳110001 [2]辽宁省人民医院内分泌科

出　　处：《中华内分泌代谢杂志》2010年第11期942-947,共6页Chinese Journal of Endocrinology and Metabolism

基　　金：基金项目：辽宁省科学技术计划项目（2007225010）;辽宁省教育厅重点实验室基金课题（20060905）;教育部高等学校博士学科点专项科研基金（新老师基金课题,20092104120003）

摘　　要：目的 探讨妊娠早期左旋甲状腺素治疗母鼠亚临床甲减对仔鼠大脑发育的影响.方法 90只Wistar雌鼠随机分成假手术对照组（C）、甲减组（CH）、亚临床甲减组（SCH）、亚临床甲减治疗Ⅰ组（妊娠第10天开始治疗,E10）、亚临床甲减治疗Ⅱ组（E13）、亚临床甲减治疗Ⅲ组（E17）,检测仔鼠体重、甲状腺功能,行水迷宫实验、Nissl染色和免疫组化染色.结果 CH组及SCH组仔鼠体重低于C组仔鼠（P＜0.05）,但E10、E13及E17治疗组体重均未受影响（P＞0.05）.各组仔鼠甲状腺功能无区别（P＞0.05）.CH、SCH及E17治疗组仔鼠逃避潜伏期比C组仔鼠延长（P＜0.05）,海马CA1区及皮质神经元排列紊乱,海马锥体层增厚,辐射层较薄,神经细胞迁移位置异常,E10及E13治疗组与C组仔鼠无区别.结论孕鼠SCH能够对后代学习记忆能力造成损害,影响细胞构筑及大脑细胞迁移,在E13之前应用左旋甲状腺素治疗可有效改善后代学习记忆能力、细胞构筑及细胞迁移.Objective To investigate the effect of treatment with levothyroxine in early maternal subclinical hypothyroidism （SCH） on the neural development of the progeny. Methods 75 thyroidectomized female Wistar rats were divided randomly into groups of hypothyroidism （CH）, SCH, SCH treated with levothyroxine at embryonic day 10 （E10）, E13, and E17. There were 15 sham operated controls. Body weight,thyroid function, and the development of progeny by morris water maze, immunohistochemistry, and Nissl＇s staining of progeny were made. Results Pups from SCH or CH group had significantly lower body weight than euthyroid group （ P〈0. 05 ）. Pups from E10, E13 or E17 groups had normal body weight compared to pups of control （P〉0.05）. The levels of TSH and total T4（ TT4 ） of all pups were normal. The mean latencies were longer in pups from CH, SCH, and E17 group than the control （P〈0.05）. The mean escape latencies did not differ between the control and E10 group pups and between the control and E13 pups （P〉0.05）. There were changes in the cytoarchitecture of the barrel cortex and of the hippocampus （ toluidine blue-stained sections） in CH, SCH, and E17 pups. The barrel cortex of E10 or E13 pups was similar to that of control pups. The distribution of BrdUlabeled cells was more widespread in CH, SCH, and E17 pups than in control, E10, and E13 progeny.Conclusion Maternal SCH disturbs learning and memory performances, cytoarchitecture and cell migration of the pups. Treatment with levothyroxine in early maternal SCH before E13 improves the cell migration in the developing brain of the progeny.

关 键 词：亚临床甲减 左旋甲状腺素 仔鼠 脑发育 

分 类 号：R686[医药卫生—骨科学]