甲状腺功能减退母鼠后代脑发育过程中microRNA的差异性表达  

The effect of maternal hypothyroidism on microRNA expression profiles in the brain of rat offsprings

作　　者：邢倩[1] 高芸 单忠艳[1] 滕卫平 

机构地区：[1]中国医科大学附属第一医院内分泌科,沈阳110001 [2]内分泌研究所,辽宁省内分泌疾病重点实验室

出　　处：《中华内分泌代谢杂志》2013年第1期69-74,共6页Chinese Journal of Endocrinology and Metabolism

基　　金：国家自然科学基金项目（30971400/H0709）;沈阳市科学计划项目（1081232,1-00）

摘　　要：目的分析甲状腺功能减退（甲减）及正常Wistar母鼠后代脑组织的差异性表达microRNA（miRNA），以探讨甲减对胎／仔鼠脑发育影响的分子机制。方法48只雌性Wistar大鼠分成2组：正常对照组（n=24），作为阴性对照；甲减组（n=24），手术完全切除甲状腺。2组雌鼠于术后1个月取血测定血清TSH及TT4，取2组妊娠13d（E13）、妊娠17d（E17）胎鼠、仔鼠出生当日（P0）及出生后7d（P7）脑组织，分离P7仔鼠的大脑海马和皮层。为减少个体差异影响，每一时间点选取2只母鼠的胎／仔鼠送检．以Affymetrix芯片进行miRNA表达谱检测。结果甲减胎／仔鼠脑组织增高2倍以上的miRNA．E13：mir-206、mir-324-5p；P7皮层：mir-34c、mir-204、mir-194；P7海马：mir-146b、mir-532—5p、mir-384—5p、mir-215、mir-212。甲减胎／仔鼠脑组织降低50％以上的miRNA，E17：mir-200b、mir-200c、mir．217、mir-672、mir-139-5p；P0：mir-376—3p；P7海马：mir-672、mir-204、mir-335、mir-376—3p。结论利用Affymetrix芯片技术对甲减胎／仔鼠脑组织进行miRNA表达谱的检测，并揭示了在甲减所致脑发育异常中miRNA的差异表达谱。Objective To analyse the differential expression of miRNAs in the brain of offsprings of hypothyroid and normal rats, and to explore the molecular mechanism underlying the effect of hypothyroidism on brain development in the offspring. Methods Forty-eight female Wistar rats were assigned to （ 1 ） control group （ n = 24 ） , and （ 2 ） hypothyroid group after complete thyroidectomy （ n = 24 ）. Serum TSH and Total thyroxine （ T4 ） were measured one month after the surgery. Brain samples of fetal or postnatal rats were obtained during four different developmental stages ： embryonic days （ E ） 13, E 17, postnatal days （P） 0 and P7. The hippocampus and cortex were separated on P7. MiRNAs were isolated from tissues and two samples were used at each time point studied to reduce the influence of individual differences. The brain samples were detected by Gene Chip miRNA arrays （Affymetrix）. Results In the brain tissues of fetal or neonatal rats of maternal hypothyroid rats, two miRNAs （ mir-206, -324-5p） on El3, three miRNAs （mir-34c, -204, -194） in cortex on P7, and five miRNAs （ mir-146b, -532-5p, -384-5p, -215, -212） in hippocampus on P7 were up-regulated by over 2 folds. Five miRNAs （ mir-200b, -200c, -217, -672, -139-5p） on El7, one miRNA （mir-376-3p） on P0, and four miRNA （ mir-672, -204, -335, -376-3p） in hippocampus on P7 were decreased by 50% or more. Conclusion The miRNA expression profiles in the rat brain of offspring with maternal hypothyroidism are characterized by miRNA arrays. The identification of a subset of brain expressed miRNAs in the brain may explain the brain development abnormalities resulting from maternal hypothyroidism.

关 键 词：妊娠 甲状腺功能减退症 微小RNA 脑 

分 类 号：R581.2[医药卫生—内分泌]