中文摘要：

目的观察胰岛素（Ins）对非肥胖糖尿病（NOD）小鼠胰岛炎和糖尿病的影响，并探讨其诱导免疫耐受的机制。方法60只NOD雌鼠随机分为胰岛素（NPH）处理组和PBS对照组，分别于第4、12、20、28周予皮下注射NPH6U（60μl）及PBS60μl十不完全弗氏佐剂60μl。于12周龄观察胰岛炎和胰岛β细胞凋亡；测定血清和脾细胞上清IL-4和干扰素（IFN）γ浓度；检测胰岛内和脾细胞IL-4、IFN-γ mRNA的表达；并行联合过继转移实验。结果Ins组糖尿病发病率和β细胞凋亡率比PBS组低。血清和脾细胞上清IL-4浓度及胰岛内和脾细胞IL-4mRNA表达较PBS组高，而IFN-γ浓度及IFN—γ mRNA表达比PBS组低。过继转移实验Ins组DM发病率比PBS组低。结论Ins能诱导NOD鼠调节T细胞的产生，使全身和胰岛局部T细胞由Th1向Th2转型，抑制β细胞凋亡，从而预防DM．

英文摘要：

Objectives To investigate the effects of subcutaneous administration of insulin on diabetes in NOD mice,and to explore the mechanism of immune tolerance induced by insulin. Methods Sixty female NOD mice were randomly divided into insulin group（n= 32 ）and PBS group（n= 28）. Insulin-treated mice were injected subcutaneously with Humulin N 6U＋IFA 60bd at 4,12,20,28 weeks of age respectively,while PBS group received PBS 60μl＋IFA 60μl, Insulitis and β cell apoptosis of islets were observed,and IL-4 and IFN-γ in sera and supernatants of spleen cells were measured. IL-4 and IFN-γ mRNA were measured by RT-PCR. Adoptive transfer tests were conducted to examine diabetes incidence. Results Insulin group versus PBS group showed the lower levels of the diabetes incidence （28. 6% vs 85.7%,P〈0.05） and apoptotie β cell rate[（1.2±0.4）% vs （6.8±1.4）%,P〈0. 05]and higher IL-4 levels of sera and spleen-cell supernatants, while IFN-7 levels were lower（all P〈0.05）. IFN-γ, mRNA levels in islets and spleen cells were lower and IL-4 mRNA levels were higher in insulin group than those in PBS group（all P〈0.05）. Adoptive transfer of diabetes study showed that the diabetes ineidenee in insulin group was lower than that in PBS group （41.7% vs 80% ,P〈0.05）. Conelusion Subcutaneous administration of insulin may induce the regulatory T cells, and make Th1 to Th2 cytokine shifts in the system and islets, thus preventing the β-cell apoptosis and the diabetes.