中国实验动物学报2025，Vol.33Issue(1)：14-22,9.DOI:10.3969/j.issn.1005-4847.2025.01.002
两种表达人促甲状腺激素受体的质粒电穿孔诱导Graves病小鼠模型的比较研究
Comparative study of two plasmid vectors expressing the human thyroid stimulating hormone receptor used to induce a mouse model of Graves'disease via electroporation
摘要
Abstract
Objective The purpose of this study was to provide a more effective method for researching the prevention and treatment of Graves'disease by comparing the effects of two plasmid vectors expressing the human thyrotropin receptor(TSHR)A subunit gene in inducing an animal model of Graves'disease via electroporation.Methods Plasmids pcDNA3.1-THSR A,and pTriEx1.1-THSR A expressing the TSHR A subunit were constructed and used to induce Graves'disease by intramuscular injection with immediate electroporation once every 3 weeks for a total of 4 times.Mice in the control group were injected with PBS.One week after the second electroporation,blood was collected to measure serum thyrotropin receptor antibody(TRAb).Three weeks following the last electroporation,echocardiography was performed on the mice.Mice were sacrificed 4 weeks after the last electroporation;blood,thyroid,and orbital tissues were collected;serum total thyroxine(TT4)was measured;and histological examination was performed.Results The average concentrations of serum TRAb in the pcDNA3.1-TSHR A group(n=15)and the pTriEx1.1-TSHR A group(n=13)were(6.9±2.0)U/L and(7.5±2.2)U/L,respectively.The latter was significantly higher than that in the control group(4.9±0.5)U/L(P=0.033).The average concentrations of serum TT4 in the pcDNA3.1-TSHR A group and pTriEx1.1-TSHR A group were(41.4±23.8)ng/mL and(63.2±53.7)ng/mL,respectively,both higher than that in the control group:(20.2±4.0)ng/mL(P＜0.01).Thyroid pathology showed thyroid follicular epithelial hyperplasia with T-cell infiltration in the model group.Echocardiography showed that the left ventricle mass in the pTriEx1.1-TSHR A group was higher than those in the control group(P=0.007)and pcDNA3.1-TSHR A group(P=0.012).Orbital pathology showed fibrotic changes in the extraocular muscles of mice in the model groups.Conclusions Both pcDNA3.1 and pTriEx1.1 expressing the TSHR A subunit were able to induce Graves'disease in mice by electroporation,and the efficiency of the two plasmids in inducing hyperthyroidism and Graves'ophthalmopathy was similar.The efficiency of pTriEx 1.1-TSHR A in inducing thyrotoxic heart disease was better than that of pcDNA3.1-TSHR A.关键词
Graves病/质粒/电穿孔/小鼠Key words
Graves'disease/plasmid/electroporation/mice分类
生物科学引用本文复制引用
林晓瑛,张萌,周星辰,吴梦芝,许华阳,王玲,伍丽萍,施秉银..两种表达人促甲状腺激素受体的质粒电穿孔诱导Graves病小鼠模型的比较研究[J].中国实验动物学报,2025,33(1):14-22,9.基金项目
国家自然科学基金(82170805,81670725,81873638,81970679).Funded by the National Natural Science Foundation of China(82170805,81670725,81873638,81970679). （82170805,81670725,81873638,81970679）
