母鼠孕期、哺乳期及子代持续高碘对子鼠甲状腺功能、记忆能力的影响  

Effects of high iodine given during pregnancy and lactation period of maternal rats and their offspring on thyroid function,memory

作　　者：王莹[1] 刘晴 姚小梅[1] Wang Ying;Liu Qing;Yao Xiaomei(Department of Physiology and Pathophysiology,Tianjin Medical University,Tianjin 300070,China)

机构地区：[1]天津医科大学生理学与病理生理学系,300070

出　　处：《中华地方病学杂志》2020年第3期163-167,共5页Chinese Journal of Endemiology

基　　金：国家自然科学基金(81874257)。

摘　　要：目的探讨大鼠孕期、哺乳期及其子代持续高碘摄入,对子代大鼠甲状腺功能和学习记忆的影响及可能机制。方法6~8周龄Wistar大鼠,体重为220~240 g,适应性喂养1周后,雌雄以1∶1交配。孕鼠分为正常碘摄入组(NI)、10倍高碘摄入组(10 HI)以及100倍高碘摄入组(100 HI),通过饮水及饲料摄碘,摄碘量分别为7.5、75.0、750.0μg/d,每组8只孕鼠,其子代断乳后继续给予不同倍数碘至180 d。利用Morris水迷宫测定子鼠空间学习记忆能力。子鼠颈总动脉取血,分离血清待测,利用酶联免疫吸附试验(ELISA)法测定血清游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)、促甲状腺激素(TSH)水平;提取海马总RNA,实时荧光定量PCR(Real-time qPCR)检测10-11易位甲基胞嘧啶双加氧酶(TET)1、2和3 mRNA表达;共聚焦免疫荧光共定位观察脑组织中甲状腺激素受体β1(TRβ1)和TET 3表达。结果与NI组[(4.95±0.53)、(12.62±1.81)pmol/L,(7.70±1.04)mU/L]相比,10 HI和100 HI组血清FT3、FT4水平[(4.60±0.49)、(4.62±0.54),(11.67±1.54)、(10.85±1.56)pmol/L]显著降低(P均<0.05),血清TSH水平[(9.62±0.93)、(9.77±1.28)mU/L]显著升高(P均<0.05)。与NI组相比,10 HI和100 HI组定位导航实验连续5 d平均逃避潜伏期显著增加(P均<0.05),第6天空间探索实验显示穿越平台次数显著减少(P均<0.05);且TET 3在海马组织中的mRNA表达显著下降(P均<0.05)。免疫荧光结果显示,TRβ1和TET 3在100 HI组子鼠脑血管壁内膜、脑室脉络丛、神经元共定位表达。结论母体孕期、哺乳期高碘摄入,子代继续高碘摄入至180 d时出现空间学习记忆能力下降,可能与甲状腺激素改变以及TET 3、TRβ1在脑中的相互作用有关。Objective The aim of this study was to investigate the alteration of thyroid function,learning and memory induced by high iodine exposure of both maternal rats during pregnancy and lactation period and their offspring and the possible mechanisms.Methods Wistar rats(6-8 weeks old,220-240 g),after one week of adaptation,female rats were mated with male rats(1∶1).Pregnant rats were divided into normal iodine intake group(NI),10 times high iodine intake group(10 HI)and 100 times high iodine intake group(100 HI),iodine uptake was 7.5,75.0,750.0μg/d through drinking water and feed,8 pregnant rats in each group.Their offspring were continuously exposed to different doses of iodine until 180 d after weaning;learning and memory ability was assessed by Morris water maze.Blood sample was taken from the common carotid artery of the offspring and serum was separated.Serum free triiodothyronine(FT3),free thyroxine(FT4),and thyroid stimulating hormone(TSH)levels were measured by enzyme linked immunosorbent assay(ELISA).Total RNA was extracted from the hippocampus of the brain and the mRNA expressions of 10-11 translocation methylcytosine dioxygenase(TET 1,TET 2 and TET 3)were detected by Real-time qPCR.The co-localized expressions of thyroid hormone receptor beta 1(TRβ1)and TET 3 in brain tissue were detected by immunofluorescence staining.Results Compared with NI group[(4.95±0.53),(12.62±1.81)pmol/L,(7.70±1.04)mU/L],in 10 HI and 100 HI groups,the levels of serum FT3 and FT4[(4.60±0.49),(4.62±0.54),(11.67±1.54),(10.85±1.56)pmol/L]were significantly decreased(P<0.05),and serum TSH levels[(9.62±0.93),(9.77±1.28)mU/L]were significantly increased(P<0.05).Compared with NI group,the average escape latency of 10 HI and 100 HI groups in the first five days was significantly increased(P<0.05),and the space exploration experiment in the sixth day showed that the number of crossing platforms was significantly decreased(P<0.05);the mRNA expressions of TET 3 in the hippocampus of the brain were significantly decreased in 10 HI

关 键 词：碘 MORRIS水迷宫 10-11易位甲基胞嘧啶双加氧酶 甲状腺激素受体 

分 类 号：R[医药卫生]