Fas-FasL在NOD小鼠胰岛炎中的作用

目的分析Fas-FasL在NOD小鼠胰岛炎中的作用。方法取32只分属不同周龄的雌性NOD小鼠,观察其血糖、胰岛HE染色、免疫组织化学染色———检测胰岛素、CD8、Fas、FasL的表达。在分析NOD小鼠胰岛炎中以胰岛或相关细胞为研究单位,从而减少了混杂因素的影响。结果雌性NOD小鼠自6周龄起出现胰岛炎,其评分逐渐增加(P<0.0005),14周龄出现糖尿病。随着胰岛炎的加重:胰岛素阳性细胞减少(P<0.0005),与胰岛炎评分呈负相关(P<0.05);Fas 胰岛细胞增加(P<0.0005),与评分呈正相关(P<0.01);FasL 胰岛细胞出现并逐渐增加(P<0.0005),与评分呈正相关(P<0.01);浸润细胞表达FasL、CD8,均逐渐增加(P<0.0005)。胰岛细胞的Fas与胰岛素表达之间呈负相关、胰岛素与FasL呈负相关、Fas与FasL呈正相关,浸润细胞的CD8与FasL表达呈正相关,P值均小于0.01。结论在NOD小鼠胰岛炎中,Fas-FasL可能参与β细胞损伤及自身免疫负调节。

Role of Fas,FasL in NOD insulitis

OBJECTIVE: To analyze the significance of Fas-FasL in NOD insulitis and to explore the mechanism of the autoimmune diabetes. METHODS: Thirty-two female NOD mice, 3-32 weeks of age, were selected. The blood glucose concentrations were recorded. The pathological data were obtained from the HE staining of the pancreatic sections and the immunohistochemical staining, in which insulin, Fas, FasL, CD8 were detected. RESULTS: Diabetes was found from the age of 14 weeks. In normal islets, insulin + cells accounted for (59.37 +/- 1.21)%, and some islet cells were observed expressing Fas. At the age of 6 weeks, insulitis lesions could be found. The average score of insulitis tended to rise with the increasing age (P < 0.0005). Meanwhile, insulin + cells decreased (P < 0.0005), and correlated negatively with scoring (P < 0.05). Fas+ islet cells increased (P < 0.0005), correlated positively with scoring (P < 0.01). In insulitis lesions, islet cells expressed FasL that increased gradually (P < 0.0005) and correlated positively with scoring (P < 0.01). The infiltrating cells were all Fas negative. But these mononucleated cells showed the expression of FasL and CD8, both increasing gradually (P < 0.0005). Furthermore, there was certain correlation between the expression of some antigens: in islet cells, between Fas and insulin (negative, P < 0.01), insulin and FasL (negative, P < 0.01), and Fas and FasL (positive, P < 0.01). In the infiltrating cells, the expression of CD8 was correlated with FasL (positively, P < 0.01); it was also found that there was a negative correlation between Fas+ islet cells and CD8+ mononucleated cells (P < 0.05). CONCLUSION: To sum up, there may be some important and complicated effects by Fas-FasL on the damage of beta cells and the regulation of autoreactive T cells in NOD insulitis, which will facilitate further studies in human type 1 diabetes.