猪甲状腺球蛋白诱导小鼠毒性弥漫性甲状腺肿模型的建立  

Preparation of mouse model of Graves disease using porcine thyroid globulin

作　　者：周驰[1] 玄振玉 邹珊珊 刘丹凤[1] 雷瑜[1] 

机构地区：[1]上海中医药大学药理学教研室,上海201203 [2]上海玉森新药开发有限公司,上海201203

出　　处：《中国药理学与毒理学杂志》2016年第5期582-587,共6页Chinese Journal of Pharmacology and Toxicology

摘　　要：目的通过注射猪甲状腺球蛋白(PTG)制备小鼠毒性弥漫性甲状腺肿(GD)模型,探索其模型发病率及稳定性。方法模型组C57BL6/N小鼠每只每周皮下多点注射PTG 25μg,共计6次。免疫攻击完成后测量心率和耗氧量;之后每2周进行血清三碘甲腺原氨酸(T3)水平的测定,以模型组小鼠血清T3水平高于正常对照组小鼠T3的x+3s为造模成功,共计12周。第12周实验结束时处死小鼠测定脾和胸腺指数、血清甲状腺球蛋白抗体和甲状腺过氧化物酶抗体,并对甲状腺组织进行病理观察。结果 PTG免疫6次后,与正常对照组小鼠相比,模型组小鼠心率加快(P<0.01),耗氧量增多(P<0.01),血清T3水平升高(P<0.01),其雄鼠发病率约为77.7%,雌鼠发病率约为88.8%。在免疫结束后的12周内,模型组血清T3水平始终高于正常对照组,雄性模型组T3水平有下降趋势,而雌性模型组血清T3始终保持相对稳定的高水平状态。结论本法制备小鼠GD模型造模时间短,发病率高,持续时间长,是较为理想的GD造模方法。OBJECTIVE To prepare the Graves disease（GD） mouse model through porcine thyroid globulin（PTG）injection and investigate the morbidity and stability of the model. METHODS C57BL6/N mice in model group received multi-point subcutaneous injection of PTG 25 μg each week,six times in all. After the end of immunization,their heart rate and oxygen consumption were measured and serum triiodothyronine（T3）level was determined every two weeks. A model was considered successful if serum T3 level was higher than x＋3s of the control group. Observation of the model lasted 12 weeks. At the12 th week,spleen and thymus gland indices,serum thyroid globulin antibodies and thyroid peroxidase antibodies were measured,and the thyroid glands were taken for pathological observation. RESULTS After six times of immunization,mice in model group showed increased heart rate（P〈0.01）,oxygen consumption（P〈0.01）and T3level（P〈0.01）compared with control group. The morbidity was 77.7% for male mice and 88.8% for females. In addition,T3 level in model group remained higher than that in control group within 12 weeks after immunization. The T3 level tended to decrease in male mice,but remained at a relatively stable higher level in females. CONCLUSION This method is suitable for GD modeling due to its short model-making time,high morbidity and long durability.

关 键 词：猪甲状腺球蛋白 毒性弥漫性甲状腺肿 动物模型 

分 类 号：R581[医药卫生—内分泌] R-332[医药卫生—内科学]