摘要
目的对比分析碘适宜和不同程度碘过量对NOD小鼠甲状腺转录组的影响,为碘过量致甲状腺自身免疫性疾病的发病机理提供科学依据。方法将40只5周龄NOD小鼠按体重分层随机分为适碘组(A)、10倍高碘组(B)、100倍高碘组(C)和1000倍高碘组(D),碘干预16周。ELISA和HE法进行血清甲功和甲状腺病理检测。RNA-seq技术对甲状腺组织转录组测序后,进行基因转录表达差异和差异基因KEGG通路的分析。结果血清甲功和甲状腺病理结果提示本实验成功建立了甲状腺正常和甲状腺不同程度病变的小鼠模型。高碘组的转录本与适碘组相比,存在950个共有表达差异基因。经KEGG分析发现,随着碘过量剂量的增加,甲状腺激素合成通路逐渐下调。与之相反,发生在信号分子相互作用和免疫系统水平的细胞因子、细胞粘附分子、趋化因子、Toll样受体和T细胞受体信号通路则被过度激活。结论碘过量在抑制甲状腺激素合成的同时,可能会过度激活多个与甲状腺自身免疫应答和病理损伤密切相关的分子通路,共同促进甲状腺功能减退和甲状腺自身免疫性疾病的发生发展。
Objective To compare and analyze the effects of iodine appropriateness and iodine overdose on thyroid transcriptome in NOD mice,so as to provide scientific basis for the pathogenesis of autoimmune thyroiditis caused by iodine overdose.Methods 405-week-old NOD mice were randomly divided into normal iodine group(A),10-fold high iodine group(B),100-fold high iodine group(C)and 1000-fold high iodine group(D)according to their body weight,and iodine intervention was performed for 16 weeks.Serum thyroid function and thyroid function were detected by ELISA and HE.RNA-seq technology was used to analyze the differences in transcription expression and KEGG pathway of different genes after sequencing thyroid transcriptome.Results The results of serum thyroid function and thyroid pathology suggested that the mouse models of normal thyroid and thyroid lesions were successfully established in this experiment.There were 950 common differentially expressed genes in the transcripts of the iodine-rich group compared with those of the normal iodine group.KEGG analysis showed that the thyroid hormone synthesis pathway was down-regulated with the increase of iodine overdose.In contrast,cytokines,cell adhesion molecules,chemokines,toli-like receptors,and t-cell receptor signaling pathways that occur at the signaling molecule interaction and immune system level are overactivated.Conclusion While inhibiting thyroid hormone synthesis,iodine overdose may overactivate several molecular pathways closely related to thyroid autoimmune response and pathological injury,jointly promoting the occurrence and development of hypothyroidism and thyroid autoimmune diseases.
作者
李亚楠
孟献亚
沈洪婷
陈勋
马静
王明君
甘培春
姜泓
何多龙
喇翠玲
胡兰盛
周昕
曹晓晓
LI Ya-nan;MENG Xian-ya;SHEN Hong-ting;CHEN Xun;MA Jing;WANG Ming-jun;GAN Pei-chun;JIANG Hong;HE Duo-long;LA Cui-ling;HU Lan-sheng;ZHOU Xin;CAO Xiao-xiao(Oinghai Institute for Endemic Disease Prevention and Control,Xining 811602,China;不详)
出处
《中国地方病防治》
CAS
2020年第4期401-405,共5页
Chinese Journal of Control of Endemic Diseases
