摘要
研究自发的 1型糖尿病雌鼠模型 (NOD)在自然状态下发生糖尿病过程中 β细胞凋亡及细胞因子TNF α、IFN γ ,诱生型NO合酶 (iNOS)和Fas、FasL在不同周龄的表达。HE法检测胰岛炎 ,免疫组化法检测各种抗体的表达 ,TUNEL法检测凋亡细胞 ,半定量法对胰岛炎评分并计数凋亡的 β细胞和各种抗体阳性细胞率 ,分析其相关性。凋亡细胞两个峰值出现在 3周和 32周 ,与周龄无关 ,与胰岛炎及血糖均相关。Fas +细胞 97 3%为胰岛细胞。FasL表达于胰岛细胞和浸润的单核细胞 ,在发病小鼠单核细胞上阳性率增高 ,FasL与血糖相关。IFN γ、TNF α的表达与周龄相关。IFN γ在晚期而TNF α持续起作用 ,但在幼鼠与成鼠不同。两种细胞因子相关。iNOS与周龄、胰岛炎及血糖均相关。β细胞主要以凋亡方式死亡 ,凋亡是多因素作用的结果。Fas FasL、NO和IFN γ、TNF α可能独自起作用 ;
To observe the progression of β cell apoptosis and the expression of TNF α, IFN γ, iNOS, Fas and Fas ligand in the islets of female NOD mice. The pancreases were fixed and embedded at different weeks after birth and then insulitis was examined by HE staining, apoptosis by TUNEL reaction and the expression of antigens by immunohistochemistry. The score of insulitis and the frequency of β cell apoptosis were recorded and antigen was detected by a semi quantitative method. The potential association between them was examined. β cell apoptosis showed two peaks, the first at week 3, which preceded the appearance of T cells (began at week 5) in the islets. The second was at week 32 when the incidence of diabetes was maximal. There was statistically significant corelation between apoptosis and insulitis / blood glucose; between FasL and blood glucose; among IFN γ, TNF α and iNOS with age. iNOS was correlated to both insulitis and blood glucose. It is suggested that apoptosis is the mode of cell death responsible for β cell deletion, and there are multiple factors responsible for the apoptosis of β cell. Fas FasL, NO. Cytokines functioned in three independent ways. IFN γ and TNF α functioned in different stages of the diabetes pathogenesis. IFN γ played a significant role in the late stage(after week 20). TNF α played a role in the pathogenesis but varied in young and adult mice.
出处
《基础医学与临床》
CSCD
北大核心
2003年第1期93-96,共4页
Basic and Clinical Medicine