目的  探讨NOD/Ltj小鼠自发1型糖尿病（T1D）过程中，胸腺内Wnt信号通路、自身免疫调节因子(AIRE)及T1D组织特异性抗原（TSAs）胰岛素2（Ins2）、谷氨酸脱羧酶67（GAD67）表达与T1D发生的关系。   方法   60只雌性 NOD/Ltj 小鼠分3组：3周组、16周未发病组及16周发病组，每组20只；非空腹血糖值连续2次≥ 11.1 mmol/L 视为发生T1D。胰腺HE染色观察胰岛炎发生情况，抗Ins、CD45免疫组织化学染色显示胰岛β细胞或浸润炎性细胞；Western blotting和Real-time PCR检测胸腺Wnt7a、β-catenin、AIRE、Ins、GAD67蛋白水平和mRNA表达；流式细胞术分析胸腺T细胞比例。   结果  1. 随着T1D发生，胰岛组织结构破坏，大量淋巴细胞浸润，残存胰岛细胞减少；Ins+胰岛β细胞周围见大量CD45+细胞聚集。2. 随年龄的增加，胸腺Wnt7a、β-连环蛋白（catenin)、AIRE、Ins和GAD67蛋白水平和mRNA表达降低；同周龄发病组小鼠与未发病组小鼠相比，胸腺Ins表达下降。3. 与3周组相比，16周未发病组CD4、CD8单阳性T细胞比例降低；16周发病组CD4、CD8单阳性T细胞比例升高，CD4、CD8双阳性T细胞比例降低。   结论  Wnt7a/β-catenin信号通路可能通过调控AIRE表达，下调T1D相关TSAs表达，参与T1D发生发展。

Objective  To investigate the relationship between the expression of Wnt signaling pathway, autoimmune regulator (AIRE) and type 1 diabetes (T1D) tissue specific antigen (TSAs) insulin 2(Ins2) and glutamic acid decarboxybase(GAD67) in thymus and the occurrence of T1D in NOD/Ltj mice with spontaneous type 1 diabetes (T1D).   Methods  Sixty female NOD/Ltj mice were divided into three groups: 3 weeks group, 16 weeks non-onset group and 16 weeks onset group. Two consecutive non-fasting blood glucose levels ≥ 11.1 mmol/L were considered as the occurrence of T1D. Pancreatic HE staining was used to observe the occurrence of islet inflammation. Anti-Ins and CD45 immunohistochemical staining showed islet β cells or infiltrating inflammatory cells. The protein levels and mRNA expressions of Wnt7a, β-catenin, AIRE, Ins and GAD67 in thymus were detected by Western blotting and Real-time PCR. The proportion of T cells in thymus was analyzed by flow cytometry.    Results  1. With the occurrence of T1D, the islet structure was destroyed, a large number of lymphocytes infiltrated, and the remaining islet cells were reduced. A large number of CD45+ cells were observed around Ins+ islet β cells. 2. The protein levels and mRNA expressions of Wnt7a, β-catenin, AIRE, Ins2 and GAD67 in thymus decreased with age. The expression of Ins in thymus decreased in the same week-old group compared with that in the control group. 3. Compared with the 3 weeks group, the proportion of CD4 and CD8 single positive T cells in the 16 weeks group was lower; In the 16 weeks group, the proportion of CD4 and CD8 single positive T cells increased, while the proportion of CD4 and CD8 double positive T cells decreased.   Conclusion  Wnt7a/β-catenin signaling pathway may be involved in the occurrence and development of T1D by regulating AIRE expression and down-regulating T1D-related TSAs expression.