小鼠亚临床甲状腺功能减退模型脂代谢相关microRNAs表达的变化  

Changes of lipid metabolism related microRNAs expression in subclinical hypothyroidism mice model

作　　者：张立亚 贾雯羽 许云云 周小明 杨锐 高聆 赵家军[1] 陈文斌[3] Zhang Liya;Jia Wenyu;Xu Yunyun;Zhou Xiaoming;Yang Rui;Gao Ling;Zhao Jiajun;Chen Wenbin(Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan 250021 , China)

机构地区：[1]山东大学附属省立医院内分泌科,济南250021 [2]山东省内分泌与脂代谢重点实验室 [3]山东大学附属省立医院科学中心

出　　处：《中华内分泌代谢杂志》2018年第5期410-415,共6页Chinese Journal of Endocrinology and Metabolism

基　　金：国家重点研究发展计划（2017YFC1309800）;国家重点基础研究计划（2012CB524900）;国家自然科学基金（81230018、81500595、81430020、81471006）

摘　　要：目的建立一种无创、简单易行的亚临床甲状腺功能减退（亚甲减）小鼠模型，并初步探索模型小鼠脂代谢相关microRNAs（miRNAs）表达的变化。方法利用甲巯咪唑（methimazole，MMI，0．08毫克／公斤体重／天）饮水喂养雄性C57BL／6小鼠建立亚甲减模型，应用实时荧光定量PCR（qPCR）检测肝脏miRNAs表达的变化。结果得到了无创、简单易行的亚临床甲状腺功能减退小鼠模型．与对照组相比．亚甲减小鼠血清促甲状腺激素（thyroid stimulating hormone，TSH）显著增加（P〈0．01），而血清游离甲状腺素（free thyroxine，FT4）水平在两组间无明显差异（P〉0．05），符合亚甲减诊断标准。亚甲减小鼠同时伴随血脂异常及肝脏脂代谢紊乱，4个脂质代谢相关miRNAs表达显著下调，亚甲减小鼠的肝脏中miR-33、miR-122、miR-199a-5p和miR-375表达水平明显低于对照组（P〈0．05）。结论本研究成功建立了无创、简单易行的亚甲减小鼠模型，发现4个肝脏脂代谢相关miRNAs差异表达，为研究亚临床甲减脂质代谢紊乱的相关机制提供了动物模型和分子基础。Objective To obtain a non-invasive subclinical hypothyroidism （SCH） mouse model, and to explore microRNAs profile related to lipid metabolism in the model mice. Methods C57BIJ6 male mice （8 weeks） were treated with methimazole （ MMI, 0.08 mg/kg BW/d） to construct SCH mouse model. MicroRNAs protiling analysis was performed by real-time quantitative polymerase chain reaction （qRT-PCR）. Results Compared with the control group, the serum thyroid stimulating hormone （TSH） in subclinical hypothyroidism group increased significantly （ P〈0.01 ）, while the serum free thyroxine （ FT4 ） level did not show significant difference between the two groups （ P〉 0. 05 ） , which was in line with the diagnostic criteria of SCH. SCH mice was accompanied by dyslipidemia and liver lipid metabolism disorders. Four lipid metabolism related miRNAs, miR-33, nliR-122, miR- 199a-5p, and miR-375 in the liver of SCH mice were significantly decreased compared with those of control （P〈 0.05 ）. Conclusion The noninvasive SCH model generated by MMI and miRNAs profile provide an animal model and a molecular basis for the study of SCH related lipid metabolism disorders.

关 键 词：亚临床甲状腺功能减退 甲巯咪唑 MICRORNAS 脂代谢 

分 类 号：R-332[医药卫生] R581.2