表达人TCRα转基因小鼠1型糖尿病模型的建立及其免疫机制的初步研究  

Preliminary study on the establishment and immunological mechanism of type 1 diabetes model in transgenic mice expressing human TCRα gene

作　　者：何君[1,2] 韩瑞红[1,2] 邓巍[1,2] 徐艳峰[1,2] 赵颖[1,2] 武岩[1,2] 李洋[1,2] 黄澜[1,2] 高虹[1,2] 高洁[1,2] 马耀文[1,2] 

机构地区：[1]中国医学科学院医学实验动物研究所,北京100021 [2]中国医学科学院糖尿病研究中心,北京100005

出　　处：《中国实验动物学报》2013年第5期82-85,F0003,共5页Acta Laboratorium Animalis Scientia Sinica

基　　金：科技部863课题"干细胞治疗糖尿病的临床前方案优化及临床应用研究"(2011AA020113);十一五重大新药创制专项(2008ZX09305-001和2009ZX09303-008)

摘　　要：目的建立T细胞介导的1型糖尿病(type 1 diabetes mellitus,T1DM)动物模型,为进一步研究该病发病免疫机理奠定基础。方法将雌雄各10只系统表达人T细胞受体α基因(T cell receptor,TCRα)小鼠随机分为模型组和对照组,其中模型组小鼠腹腔注射链脲佐菌素(streptozotocin,STZ)每次100 mg/(kg·bw),间隔1 d后再注射一次,对照组注射等量的生理盐水;注射后每周测定一次血糖和体重,当出现重度糖尿病临床表现时处死,其余小鼠注射后8周处死,观察胰腺组织病理学改变,并进行外周血淋巴细胞亚群,以及血清胰岛素和细胞因子的测定。结果模型组小鼠发病率为10/10,对照组为0/10;模型组外周血T细胞亚群CD3+、CD4+、CD8+、CD4+/CD8+水平较对照组均有显著降低(P<0.01),B细胞表型CD19+水平与对照组差异无显著性(P>0.05);注射STZ后约8周,模型组血清胰岛素、IFN-γ、TNF-β较对照组差异有显著性(P<0.01),IL-2高于对照组但差异无显著性(P>0.05)。结论在系统表达人TCRα基因小鼠腹腔注射链脲佐菌素(STZ)后2～8周可建立稳定1型糖尿病的小鼠模型。Objective To establish a type 1 diabetes model in transgenic mice expressing human TCRα gene for investigation of the pathogenesis of type 1 diabetes. Methods Twenty TCR transgenic mice （ male： female = 1 ： 1 ） were randomly divided into two groups. The experimental group was induced by intraperitoneal injection of streptozotiocin （ 100 mg/kg/time） , and the control group was injected with the same amount of saline. Both groups were injected twice with an interval of 48 h. The blood glucose level and body weight were measured weekly. The mice were killed when they had significant clinic symptoms or 8 weeks after STZ injection, followed by pathological examination and serum insulin and cytokine assays. Results The incidence of diabetes in the experimental group was 10/10 whereas that of control group was 0/ 10. The level of CD3^＋, CD4^＋, CD8^＋, and the relation between CD4^＋ and CD8^＋ T-cells were significantly changed between the experimental and control groups. The contents of insulin,IFN-γ and TFN-β were changed significantly between the experimental and control groups. The level of IL-2 of the experimental group was higher than that in the control group, but not significantly increased. Conclusion Stable type 1 diabetes model can be successfully established in transgenic mice expressing human TCRot gene within 2 - 8 week after i.p. injection of streptozotocin.

关 键 词：1型糖尿病 动物模型 转人TCRα基因小鼠 

分 类 号：Q95-33[生物学—动物学]