不同条件下建立自身免疫性甲状腺炎小鼠模型的比较研究  

Mouse models of experimental autoimmune thyroiditis under different conditions:a comparative study

作　　者：丁习 赵洋 伍丽萍[1] 吕宏军[1] 许华阳 周一坤 施秉银[1] DING Xi;ZHAO Yang;WU Liping;LYU Hongjun;XU Huayang;ZHOU Yikun;SHI Bingyin(the First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061,China)

机构地区：[1]西安交通大学第一附属医院,西安710061

出　　处：《中国实验动物学报》2022年第4期449-458,共10页Acta Laboratorium Animalis Scientia Sinica

基　　金：国家自然科学基金(81500597)。

摘　　要：目的观察和比较不同性别、抗原剂量、注射频次结合造模时长对猪甲状腺球蛋白(porcine thyroglobulin,pTg)诱导的小鼠实验性自身免疫性甲状腺炎(experimental autoimmune thyroiditis,EAT)模型建立的影响。方法SPF级80只CBA/J小鼠,在不同性别(雌性60只,雄性20只),不同抗原剂量(pTg 50、100、200μg),不同注射频次结合造模时长(28 d内注射2次,28 d内注射3次及35 d内注射3次)条件下构建EAT小鼠模型。通过甲状腺病理评分、血清抗甲状腺球蛋白抗体TgAb滴度、血清总甲状腺素TT4水平、脾Treg及Th17细胞比例及相关转录因子水平比较造模的效果。结果(1)相同造模条件下雄性小鼠甲状腺淋巴细胞浸润程度及EAT评分均低于雌鼠,TgAb滴度、Th17细胞比例及IL-17A表达水平均较雌鼠显著降低;(2)50μg造模组TgAb滴度、TT4水平、Th17细胞比例、转录因子RORγt及IL-17A的表达量均显著低于100μg造模组;200μg造模组Foxp3表达量显著高于100μg造模组;(3)28 d 3次造模组甲状腺病理评分较常规造模组显著升高,TgAb、TT4水平、Th17细胞比例、转录因子RORγt及IL-17A的表达量均显著升高,Treg细胞比例显著降低。结论选择雌性CBA/J小鼠、增大抗原剂量、短期内增加造模频次对改进EAT造模效果具有重要作用。Objective To observe and compare the effects of sex,antigen dose,injection frequency,and modeling time on a porcine thyroglobulin(pTg)-induced experimental autoimmune thyroiditis(EAT)mouse model.Methods A total of 80 SPF CBA/J mice were selected to establish an EAT model under various conditions:sex(60 females and 20 males),antigen dose(pTg 50μg,100μg,and 200μg),and injection frequency and modeling duration(two injections in 28 days,three injections in 28 days,or three injections in 35 days).The effects of the different modeling strategies were compared using thyroid pathology scores,serum TgAb titers,serum TT4 levels,proportions of Treg and Th17 cells in the spleen,and the levels of related transcription factors.Results(1)Under the same modeling conditions,the degree of thyroid lymphocyte infiltration and EAT scores were lower,and the TgAb titers,proportion of Th17 cells,and IL-17A expression levels were significantly lower,in male mice than female mice.(2)TgAb titers,TT4 levels,proportion of Th17 cells,and expression levels of RORγt and IL-17A in the 50μg model group were significantly lower than those in the 100μg model group,and the expression level of Foxp3 in the 200μg model group was significantly higher than that in the 100μg model group.(3)EAT scores,TgAb titers,TT4 levels,proportion of Th17 cells,and expression levels of RORγt and IL-17A were significantly increased,and the proportion of Treg cells was significantly decreased,in the three injections in 28 days group.Conclusions Selecting female CBA/J mice,increasing the antigen dose,increasing the modeling frequency and reducing the modeling time improved the EAT modeling effect.

关 键 词：自身免疫性甲状腺炎 猪甲状腺球蛋白 性别 注射频次 小鼠 

分 类 号：Q95-33[生物学—动物学]