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目的不同剂量谷氨酸脱羧酶(GAD)对非肥胖型糖尿病小鼠(NOD)糖尿病免疫干预效果的影响。方法将3周龄40只体重(10.0±0.9)g雌性NOD小鼠分为4组分别腹腔注射GAD0.3mU和不完全弗氏佐剂(IFA)50μL、GAD3mU+IFA50μL、GAD0.03mU+IFA50μL、IFA50μL。8周龄时注射环磷酰胺200mg/kg加速糖尿病,定期检测血糖,眼内眦取血分离血清检测细胞因子白细胞介素(IL)4和干扰素(IFNγ)的变化,动态观察各组糖尿病发生发展的过程。28周时,全部处死,取脾、胸腺作淋巴细胞亚群测定,胰腺作病理组织学观察。结果GAD3mU+IFA50μL组小鼠无一只发生糖尿病,28周时血糖为(5.0+1.1)mmol/L;胰岛个数最多(8.2+2.3)个/张(P<0.01),胰岛炎评分最低(0.33+0.12)(P<0.01);血清中IL4的水平最高为(80+6)ng/L(P<0.01),IFNγ水平最低为(327±48)ng/L;CD8+/CD4+比值最大(P<0.01),在脾脏中为0.524±0.133,胸腺中为0.428±0.021。结论NOD小鼠在3周龄时腹腔注射CAD3mU+IFA50μL混合物比其他剂量组免疫调节效果好,较好地通过调节胸腺,脾淋巴细胞亚群分类,并通过淋巴细胞分泌Th1类因子和Th2类因子来调节Th0细胞的转化,从而抑制NOD小鼠胰岛炎,胰岛β细胞破坏减少,GAD3mU剂量组免疫干预NOD小鼠糖尿病的发生效果最好。
Objective To investigate the effect of different dosages of glutamic acid decarboxylase (GAD) on diabetic immune response in non-obese diabetic mice (NOD). METHODS: Forty three-week-old female NOD mice weighing 10.0 ± 0.9 g were divided into 4 groups: intraperitoneal injection of 50 μL of GAD 0.3 mU and incomplete Freund’s adjuvant (IFA), 50 μL of GAD3mU + IFA, 50 μL of GAD 0.03 mU + IFA, IFA 50μL. At 8 weeks of age, cyclophosphamide (200mg / kg) was injected to accelerate the diabetes mellitus, blood glucose was measured regularly, serum from the intraocular 眦 blood was collected to detect the changes of cytokines such as interleukin (IL) 4 and interferon (IFNγ) Development process. At 28 weeks, all sacrificed, spleen and thymus were taken as lymphocyte subsets, and the pancreas was observed for histopathology. Results None of the mice in the GAD3mU + IFA group had diabetes mellitus at the 28th week. The blood glucose was (5.0 + 1.1) mmol / L at the 28th week, the number of islets was (8.2 + 2.3) (P <0.01). The level of IL4 in serum was the highest (80 ± 6) ng / L (P <0.01), the lowest was IFNγ (327 ± 48) ng / L and the ratio of CD8 + / CD4 was the highest P <0.01), 0.524 ± 0.133 in the spleen and 0.428 ± 0.021 in the thymus. CONCLUSION: The NOD mice were injected intraperitoneally with CAD3mU + IFA 50μL mixture at 3 weeks of age. The immunomodulatory effect was better than that of other dose groups. By adjusting the classification of thymus and spleen lymphocyte subsets and secreting Th1-type and Th2-type cytokines To regulate the transformation of Th0 cells, thereby inhibiting insulitis in NOD mice, reducing islet β cell destruction, GAD3mU dose of immune intervention NOD mouse diabetes the best.