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
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国家高技术研究发展计划(863计划)

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    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20只系统表达人T细胞受体α基因(T cell receptor,TCRα)小鼠随机分为两组, 模型组小鼠腹腔注射链脲佐菌素(streptozotocin, STZ)100mg/kg体重/次,间隔1天后再注射一次,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 水平与对照组无显著性差异( P> 0. 05);注射STZ后约8周,模型组血清胰岛素、IFN-γ、TNF-?较对照组有显著性差异(P?0.01),IL-2高于对照组但无无显著性差异( 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。

    Abstract:

    Objective:To establish type 1 diabetes model in transgenic mice expressing human TCRα gene for investigating the pathogenesis of type 1 diabetes. Methods: 20 TCR transgenic mice were randomly divided into two groups. One was experimental group induced by intraperitoneal injection of STZ (100 mg/kg/times), the other was control group injected with the same amount of saline. Two groups were injected two times with an interval of 48h. The blood glucose levels and weight were detected weekly. The mice were killed when they had significant clinic appearance or 8 weeks after STZ injection, followed by pathologic studies and serum insulin,cytokine assays. Results:The incidence of experimental group was 10/10 whereas that of control group was 0/10. The level of CD3 ,CD4 ,CD8 ,the relation between CD4 and CD8 T-cells were changed significantly between experimental group and control group. The amounts of insulin,IFN-γ,TFN-? were changed significantly between experimental group and control group. The amount of IL-2 of experimental group was higher than control group, but there was no significant difference. Conclusion:Model mice of type 1 diabetes can be established in transgenic mice expressing human TCRα gene during the 2~ 8 week after i.p injection with STZ.

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何君,韩瑞红,邓巍,徐艳峰,赵颖,武岩,李洋,武鑫,秦超,卢星辰,李名烁,金翠英,黄澜,高虹,高洁,马耀文.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[J].中国实验动物学报,2013,21(5).

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  • 收稿日期:2013-05-18
  • 最后修改日期:2013-07-02
  • 录用日期:2013-07-24
  • 在线发布日期: 2013-10-18
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