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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 an animal model of T cell-mediated type 1 diabetes mellitus (T1DM) and lay a foundation for further study on the pathogenesis and pathogenesis of this disease. Methods T-cell receptor (TCRα) mice were randomly divided into model group and control group. The mice in model group were intraperitoneally injected with streptozotocin (STZ) Each 100 mg / (kg · bw) injection was performed one d after the interval and the control group was injected with the same amount of saline. Blood glucose and body weight were measured once a week after injection. The mice were sacrificed in the presence of clinical manifestations of severe diabetes. The remaining mice The mice were sacrificed at 8 weeks after the injection and pathological changes of the pancreas were observed. Peripheral blood lymphocyte subsets, serum insulin and cytokines were measured. Results The incidence rate of mice in model group was 10/10 and that in control group was 0/10. The levels of CD3 +, CD4 +, CD8 + and CD4 + / CD8 + of T cell subsets in model group were significantly lower than those in control group (P <0.01) The level of CD19 + in B cell was not significantly different from that in control group (P> 0.05). The levels of serum insulin, IFN-γ and TNF-β in model group were significantly different from those in control group after about 8 weeks of STZ injection (P <0.01) , IL-2 higher than the control group but no significant difference (P> 0.05). Conclusions A mouse model of stable type 1 diabetes can be established 2 to 8 weeks after systemic injection of streptozotocin (STZ) into human TCRα mice.