融合蛋白HSP65-6 ×P277 在NOD 鼠中降糖作用的机制研究

摘要/Abstract

摘要： 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。

关键词: 热休克蛋白65, p277 肽, Th1/Th2 细胞, 细胞因子

Abstract: 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)-γsecretion. 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.

Key words: heat shock protein 65, P277, Th1/Th2 cells, cytokines

中图分类号:

R965

金亮, 王宇, 朱爱华, 刘景晶. 融合蛋白HSP65-6 ×P277 在NOD 鼠中降糖作用的机制研究[J]. 中国临床药理学与治疗学, 2009, 14(10): 1142-1150.

JIN Liang, WANG Yu, ZHU Ai-hua, LIU Jing-jing. Study on the hypoglycemic mechanism of the fusion protein HSP65 -6 ×P277 in NOD mice[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(10): 1142-1150.

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