目的:探讨融合蛋白HSP65-6×P277在NOD鼠中的降糖作用机制。方法:融合蛋白HSP65-6×P277通过鼻腔给药方式,在不添加任何佐剂的情况下3次免疫4周龄雌性NOD小鼠。观察该融合蛋白对NOD小鼠血糖,细胞因子水平,抗体类型和胰腺炎严重程度的影响。结果:融合蛋白HSP65-6×P277免疫组动物血清中含有高水平的IL-4和低水平的IL-2 ,P277特异性抗体类型主要为IgGl和IgG2b,IgG2a水平较低;T细胞增殖实验的培养上清中含有较高水平的IL-10和较低水平的IFN-γ;胰腺炎的严重程度和1型糖尿病的发病率显著降低。结论:诱导了Th2免疫反应可能是HSP65-6×P277预防1型糖尿病发生的作用机制之一。
AIM:To evaluate the hypoglycemic mechanism of the fusion protein HSP65-6×P277 in NOD mice.METHODS:The fusion protein was used to immunize 4-week old female NOD mice with three i.n.inoculations in the absence of adjuvants.The effects of HSP65-6×P277 on NOD mice were investigated by observing the change of blood glucose,cytokine levels,antibody types and degree of insulitis.RESULTS:The sera collected from HSP65-6×P277 treated mice,contained relatively high levels of interleukin IL-4 but low levels of IL-2,and the antibody types were almost exclusively of the IgGl and IgG2b subclass,but at very low levels of IgG2a.T cells from HSP65-6×P277 treated mice when incubated with HSP-peptide conjugate showed an increase in IL-10 secretion and a decrease in interferon (IFN)-γ secretion.HSP65-6×P277 treatment reduced insulitis and T1DM incidence.CONCLUSION:The hypoglycemic mechanism of the fusion protein HSP65-6×P277 is related to its inducing Th2 responses.