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目的 观察雌性非肥胖糖尿病 (NOD)小鼠口服胰岛素和谷氨酸脱羧酶 (GAD)对糖尿病发生的影响 ,以及对白细胞介素 4(IL 4)的血清水平和胰腺IL 4mRNA转录的影响。方法 雌性NOD小鼠分为 3组 :第一组给予PBS作为对照组 ,第二组给予胰岛素 ,第三组予以GAD。ELISA法检测血清IL 4水平 ,Northern杂交检测胰腺IL 4mRNA的表达。结果 胰岛素或GAD均能抑制NOD小鼠糖尿病的发生 ,PBS组 14周龄起病 ,胰岛素组和GAD组则 2 6周龄起病 ,5 2周龄时糖尿病的累积发病率对照组为 89.4% ,胰岛素组和GAD组分别为 6 6 .6 %和 6 4.7% (P <0 .0 1)。口服胰岛素和GAD能促进血清IL 4的水平增加 ,对照组 12周龄时血清IL 4水平 (6 4.5 2± 6 .89) μg/L ,而胰岛素组为 (77.94± 8.12 ) μg/L ,GAD组 (83.10± 9.6 3) μg/L ,胰岛素组和GAD组显著低于对照组 (P <0 .0 1)。Northern杂交检测胰腺IL 4mRNA发现胰岛素组可见IL 4mRNA的表达 ,PBS组未见表达。结论 口服胰岛素、GAD可预防NOD小鼠发生糖尿病 ,其机制可能与诱导的Th2 型细胞因子局部和全身表达的增加有关。
Objective To investigate the effects of oral administration of insulin and glutamic acid decarboxylase (GAD) on the development of diabetes in female non-obese diabetic (NOD) mice and the effects of interleukin 4 (IL 4) serum levels and pancreatic IL 4 mRNA transcription. Methods Female NOD mice were divided into 3 groups: the first group received PBS as the control group, the second group received insulin, and the third group received GAD. Serum IL-4 levels were detected by ELISA, and the expression of IL-4 mRNA was detected by Northern blot. Results Both insulin and GAD could inhibit the onset of diabetes in NOD mice. The PBS group was onset at 14 weeks of age, insulin group and GAD group was 26 weeks old, and the cumulative incidence of diabetes at 52 weeks was 89.4% , Insulin group and GAD group were 6.6% and 6.7% (P <0.01) respectively. Oral insulin and GAD promoted the increase of serum IL-4 level. Serum IL-4 level (6 4.5 2 ± 6. 89) μg / L at 12 weeks of the control group and (77.94 ± 8.12) μg / L insulin group, GAD Group (83.10 ± 9.63) μg / L, insulin group and GAD group was significantly lower than the control group (P <0.01). Northern blot analysis of IL-4 mRNA in the pancreas revealed the expression of IL-4 mRNA in the insulin group and no expression in the PBS group. Conclusion Oral insulin and GAD can prevent diabetes in NOD mice. The mechanism may be related to the increase of local and systemic expression of Th2 cytokines.