摘要
目的 观察腹腔注射胰岛素或B链肽 (9～ 2 3)对NOD鼠胰岛FasL/Fas系统表达的影响。 方法 96只雌性NOD鼠随机分为B1、B2和B3三组 ,每组 32只。于 4周龄分别腹腔注射胰岛素、胰岛素B链肽和PBS ,15周龄检测胰腺Fas、FasL、CPP32蛋白 ,及IFN γ、IL 10、Fas、FasL和CPP32mRNA的表达水平。并观察 30周龄糖尿病的累积发病率。 结果 B1组和B2组较B3组糖尿病初发时间延迟 (2 2、2 4、17周 ) ,发病率下降 (37%、32 %、72 % ) ,胰岛炎积分明显减轻 (P <0 0 1) ,胰腺IFN γ、Fas、CPP32mRNA的表达 ,B1组和B2组较B3组明显减弱 (P <0 0 1) ,B1组和B2组胰腺IL 10的表达较B3组明显增强 (P <0 0 1) ,FasLmRNA的表达三组间均无统计学差异 ;胰岛细胞及炎症细胞Fas、CPP32蛋白表达 ,B1组和B2组明显弱于B3组 (P <0 0 5 )。FasL蛋白在胰岛细胞和炎症细胞的表达 3组间无统计学差异 (P >0 0 5 )。 结论 胰岛素和胰岛素B链肽免疫NOD鼠可下调Th1细胞和细胞因子效应 ,上调Th2细胞和细胞因子效应 ,进而下调胰岛 β细胞和炎症细胞FasL/Fas凋亡通路 ,延缓糖尿病发病。
Objective Immune tolerance was induced by intraperitoneal injecting insulin and B chain peptide in 4 week old NOD mices Method 96 female NOD mices were randomly divided into B1, B2 and B3 groups, which were injected respectively by insulin, B chain peptide and PBS at 4th week Twelve mice of each group were killed at 15th week to mesaure the mRNA levels of IFN γ, IL 10 , Fas, FasL and CPP32, as well as Fasl, Fas and CPP32 protein in pancreas Twenty mice were used to evaluate incidence of diabetes Results The onset of diadetes delayed (by 22,24,16W), incidence of diabetes decreaded (37%,32%,72%) and mean insulitis score were significantly lower ( P<0 01 ) in B1 and B2 than B3 group The levels of IFN γ,Fas and CPP32 mRNA expressed stronger in B1 or B2 than B3 ( P<0 01 ) Although the expression of FasL mRNA was stronger in B1 than B3, there were not significant differences among three groups Expressions of Fas and CPP32 proteins were weaker markedly in B1 and B2 vs B3 ( P<0 05 ) Levels of FasL proteins were not different among three groups ( P>0 05 ) in islet cells and infiltrating inflammatory cells Conclusion Early using insulin or β chain peptide can prevent NOD mice from diabetes by down regulating Th1 cell response , and up regulating Th2 cell response, as well as down regulating expression of FasL/Fas system on islet β cells and inflammatory cells
基金
国家自然科学基金资助项目 (3 0 0 70 3 65 )
山西省自然科学基金资助项目 (2 0 0 2 110 9)
