大鼠妊娠期母体亚临床甲状腺功能减退下调后代海马胰岛素样生长因子Ⅰ通路相关蛋白水平  

Maternal subclinical hypothyroidism during pregnancy down-regulates insulin-like growth factor Ⅰ signaling pathway on hippocampus in rat offspring

作　　者：范雨鑫 张媛媛[1] 暴素青 范晨玲[1] 滕卫平[1] 单忠艳[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辽宁省内分泌疾病重点实验室,沈阳110001

出　　处：《中华内分泌代谢杂志》2014年第12期1068-1073,共6页Chinese Journal of Endocrinology and Metabolism

摘　　要：目的 探究妊娠期母体亚临床甲状腺功能减退（甲减）是否可以导致后代仔鼠海马胰岛素样生长因子Ⅰ （IGF-Ⅰ）、胰岛素样生长因子Ⅰ受体（IGF-Ⅰ R）和磷酸化蛋白激酶B（p-Akt）的表达降低,进而影响后代空间学习和记忆能力.方法 60只SPF级雌性Wistar大鼠随机分成3组,正常对照组（CON）20只,亚临床甲减组（SCH）20只,甲减组（CH）20只.仔鼠出生后的第3天和第7天冰上断头,分别取海马组织,以实时定量PCR方法检测IGF-Ⅰ mRNA表达,以ELISA方法检测IGF-Ⅰ、IGF-Ⅰ R蛋白表达,以Western印迹方法检测蛋白激酶B（Akt）及p-Akt蛋白表达.仔鼠出生后第40天行Morris水迷宫行为学检测及海马兴奋性突触后电位长时程增强检测.结果 与正常对照组仔鼠相比,亚临床甲减组仔鼠海马IGF-Ⅰ mRNA水平的表达在第3天和第7天时降低幅度分别为27％ （P＜0.01）和21％ （P＜0.01）,IGF-Ⅰ蛋白含量的表达降低幅度分别为29％（P＜0.01）和25％ （P＜0.01）,IGF-Ⅰ R蛋白的表达在第3天和第7天时降低幅度约为23％ （P＜0.01）和19％ （P＜0.05）,p-Akt蛋白的表达在第3天和第7天时降低幅度约为19％（P＜0.01）和11％ （P＜0.05）.与甲减组相比,仔鼠IGF-Ⅰ mRNA水平的表达和IGF-Ⅰ蛋白含量的表达在第3天和第7天时均增高（P＜0.05）,而IGF-Ⅰ R和总Akt蛋白含量的表达在第3天时高于甲减组（P＜0.05）,而在第7天时与甲减组表达无统计学差异（P＞0.05）.第40天时,对仔鼠进行Morris水迷宫定位航向检测,各组仔鼠的逃避潜伏期均随训练天数的增加而缩短.甲减组的逃避潜伏期始终长于正常对照组.亚临床甲减组的逃避潜伏期在第1、2天与正常对照组无明显差异（P＞0.05）,第3、4天逃避潜伏期长于正常对照组,有统计学差异（P=0.034;P=0.047）.在第40天时对仔鼠进行兴奋性突触后电位长时程增强检测,海马经强直刺激后各组仔鼠兴奋性�Objective To investigate the effect of subclinical hypothyroidism during pregnancy on hippocampus insulin-like growth factor Ⅰ （IGF-Ⅰ） signaling pathway in rat offspring.Methods A total of 60 female Wistar rats were evenly divided into control（CON）,subclinical hypothyroidism（SCH）,and clinical hypothyroidism （CH） groups.The hippocampus of progenies were collected on the postnatal day 3,postnatal day 7 to measure protein kinase B （Akt） and phosphorylated-Akt （p-Akt） by Western blot,IGF-Ⅰ and insulin-like growth factor Ⅰ receptor （IGF-Ⅰ R） by Elisa.Morris water maze and field excitatory postsynaptic potential long-term potentiation were measured at the postnatal 40 day.Results Western blot and Elisa revealed that levels of IGF-Ⅰ,IGF-Ⅰ R,and p-Akt of pups from SCH group were lower than that of CON group and were higher than CH group on day 3 （P ＜ 0.05）.On day 7,the levels of IGF-Ⅰ,IGF Ⅰ R,and p-Akt of pups from SCH group were lower than CON group （P＜ 0.05）,but no difference was observed in p-Akt and IGF-Ⅰ R level between SCH group and CH group （P ＞ 0.05）.Latencies of all groups had shortened in Morris water maze test with increasing of training trials.The slope of field excitatory postsynaptic potenial was increased in all groups after Theta burst stimulation.The amplification percentage of slope of field excitatory postsynaptic potenial in SCH group＇s was lower than control group＇s but was higher than CH group＇s（all P values＜0.05）.Conclusions Maternal subclinical hypothyroidism impairs long-term potentiation induction in hippocampus of rat might be associated with the levels of IGF-Ⅰ,IGF-Ⅰ R,and p-Akt.

关 键 词：妊娠 亚临床甲状腺功能减退症 胰岛素样生长因子Ⅰ 胰岛素样生长因子Ⅰ受体 磷酸化蛋白激酶B MORRIS水迷宫 长时程增强 

分 类 号：R714.256[医药卫生—妇产科学]