Ad-TSHR289诱导Graves病模型小鼠导致肾脏病变的研究  

Study on renal lesion induced by Ad-TSHR289 in Graves disease model mice

作　　者：荀利如[1] 伍丽萍[2] 白旭升[3] 孙亚丽[3] 李振江[1] 王晓明[1] 高妍婷[1] 孙燕[1] XUN Liru;WU Liping;BAI Xusheng;SUN Yali;LI Zhenjiang;WANG Xiaoming;GAO Yanting;SUN Yan(Center of Hemodialysis and Nephrosis,Shaanxi Provincial People′s Hospital,Xi′an,710068,China;Department of Endocrinology,The First Affiliated Hospital,Xi′an Jiaotong University,Xi′an 710061,China;;Department of Pathology,Shaanxi Provincial People′s Hospital,Xi′an 710068,China)

机构地区：[1]陕西省人民医院肾病血透中心,西安710068 [2]西安交通大学第一附属医院内分泌科,西安710061 [3]陕西省人民医院病理科,西安710068

出　　处：《新疆医科大学学报》2018年第10期1273-1276,共4页Journal of Xinjiang Medical University

基　　金：陕西省自然科学基础研究计划项目(2014JM4155)

摘　　要：目的采用编码TSH受体A亚单位的腺病毒(Ad-TSHR289)免疫制备Graves病模型小鼠,探讨Graves病小鼠肾脏病理变化。方法 10只BALB/c小鼠用Ad-TSHR289免疫(模型组),另取5只BALB/c小鼠用Ad-lacz免疫(对照组)。将腺病毒分别经后臀部肌肉注射,每3周注射1次,共3次,第3次免疫后6w采血,检测血清促甲状腺素受体抗体(TRAb)、总甲状腺素(TT4)和促甲状腺素(TSH),剥离甲状腺、肾脏,行石蜡包埋、切片、HE染色,组织学检查。结果 75.0%的小鼠TRAb水平升高,37.5%TT4升高,TRAb升高的小鼠中83.3%(5/6)伴有甲状腺组织增生,其中62.5%的小鼠肾脏组织发生变化,其中大部分为膜性肾病表现,而且均有TRAb升高。从喂养第6周开始(即第2次免疫后)模型组小鼠体质量明显低于对照组。结论用Ad-TSHR289免疫小鼠可成功建立Graves病动物模型,并可观察到GD相关性肾病的表现,为进一步研究GD相关性肾病提供了良好的工具。Objective The Graves disease(GD)model mice were immunized with adenovirus encoding the TSH receptor A subunit(Ad-TSHR289)to investigate the pathological changes of the kidney in GD mice.Methods The BALB/c female mice with 6-8 weeks in model group were immunized with Ad-TSHR289,while the control group was immunized with Ad-lacz.Adenoviruses were injected through the gluteal muscles respectively.They were injected for 3 times with 1 time per 3 weeks.Blood samples were collected at the sixth week after the third immunization.The levels of serum thyrotrophin receptor antibody(TRAb),total thyroxine(TT4)and thyroid stimulating hormone(TSH)were detected.The thyroid and kidneys were stripped,embedded using paraffin,sliced and stained by HE,and then histological examination was performed.Results The level of TRAb was increased in 75%of the mice,and the level of TT4 was increased in 75.0%of the mice.83.3%(5/6)mice with increase of TRAb appeared hyperplasia of thyroid gland,62.5%of them presenting nephropathologic change,in which most of them were membranous nephropathy with increase of TRAb.The body weight in the model group were significantly lower than that in the control group from the 6th week after feeding(ie,after the second immunization).Conclusion The animal model with GD was successfully established by using Ad-TSHR289 to immunize mice.Characterization with GD related nephropathy was observed in GD mice.This study could provide a good tool for further study of GD related nephropathy.

关 键 词：自身免疫性甲状腺疾病相关性肾病 Ad-TSHR289 甲状腺功能 肾脏病理 

分 类 号：R781.6[医药卫生—口腔医学]