口服胰岛素、谷氨酸脱羧酶对NOD小鼠糖尿病发生率的影响

Effects of oral administration of insulin and glutamic acid decarboxylase on the incidence of diabetes mellitus in non-obese diabetic mice

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 observe the diabetes preventing effects of oral administration of recombinant human insulin and glutamic acid decarboxylase (GAD) to female non obese diabetic (NOD) mice. The IL 4 mRNA transcription of pancreatic islet and serum IL 4 level before and after the oral antigen feeding were determined. Methods 96 female NOD mice were divided into three groups. Group 1: orally administrated PBS; Group 2: orally given insulin; Group 3: orally given GAD. The whole observation lasted one year. Serum IL 4 was measured by ELISA and IL 4 mRNA transcription of pancreatic islet was examined by Northern blot. Results Oral administration of insulin to female NOD mice significantly suppressed incidence of diabetes. The PBS group became overt diabetes starting from 14 weeks of age while diabetes occurred in insulin and GAD groups at the age of 26 weeks. Diabetes incidences of PBS group, insulin group and GAD group were 89.4%, 66.6% and 64.7% respectively at the age of 52 weeks (P<0.01). Serum IL 4 level in NOD mice was elevated after oral administrated insulin and GAD at 12 and 16 weeks compared to control group 〔(77.94±8.12)μg/L, (83.10±9.36)μg/L vs (64.52±6.89)μg/L at 12 weeks, P all <0.01〕. IL 4 mRNA was transcripted in pancreas from insulin fed mice but not from PBS fed group. Conclusion These results show that the oral insulin and GAD administration can prevent NOD mice from diabetes. Pancreatic and systematic expression of Th 2 type cytokine may play an important role assooiating with the preventing effect.