摘要
目的 探讨NOD小鼠胰岛 β细胞凋亡的规律及完全弗氏佐剂 (CFA)在预防胰岛炎和糖尿病中的作用。方法 计数 12天龄、6周龄、12周龄未处理的NOD雌鼠胰岛 β细胞的凋亡。将 3周龄NOD雌鼠随机分入CFA组、PBS对照组 ,分别给予后足板一次性注射CFA 5 0 μl、PBS 5 0 μl,于 6周龄、12周龄、30周龄时 ,观察胰岛 β细胞凋亡率 ,胰岛炎程度和糖尿病发病率。 结果 未处理组 12天龄胰岛 β细胞凋亡率分别高于 6周龄、12周龄 (P <0 .0 1)。 6周、12周时CFA组胰岛炎积分 ,β细胞凋亡率均明显低于同期PBS组 (P <0 .0 5 ,P <0 .0 1) ,6周龄、12周龄胰岛炎积分与 β细胞凋亡率存在正相关 (r =0 .5 9,P <0 .0 1)。到 30周龄时 ,CFA组糖尿病发病率 (9.1% )较PBS组 (81.8% )明显降低 (P=0 .0 0 1)。结论 早期给予NOD鼠CFA可明显减轻胰岛炎和预防糖尿病的发生 ,其机制与抑制 β细胞凋亡有关。
Objective To investigate the natural course of the islet β cell apoptosis and the preventive effect of complete Freund′s adjuvant (CFA) from insulitis and diabetes in NOD mice. Methods Apoptotic β cells were counted in 12 day old, 6 week old, and 12 week old untreated female NOD mice respectively. Three week old female NOD mice were divided into CFA group and phosphate buffer saline (PBS) group, and 50 μl CFA or 50 μl PBS was respectively injected once into the pad of hind foot. Two groups of mice were sacrificed at 6 week, 12 week and 30 week of age respectively, and the apoptotic rate of β cells in islets, insulitis degree and diabetes incidence were observed. The pancreatic sections were stained with hematoxylin and eosin to score insulitis, and the apoptotic rate of β cells in islets were confirmed with the di labeling technique of the TUNEL in situ end labeling method combined with standard sensitive avidinbiotin complex (sABC) immunohistochemical method. Results The apoptotic rates of β cell at 12 day of age was higher than that at 6 week or 12 week in untreated group (P<0.01). The insulitis score and the apoptotic rate of β cells of CFA treated mice at 6 and 12 week of age were significantly lower than thoseofPBS treated miceatthe corresponding age respectively (P<0.05, P<0.01 respectively). The positive correlations were foundbetweentheapoptoticrateof β cells and the insulitis score at 6 week and 12 week of age (r=0.59,P<0.01). The diabetes incidence in CFA treated mice (9.1%)waslowerthanthatin PBS treated mice (81.8%) (P=0.001). Conclusion CFA treated at early age can diminish insulitis and prevent the development of autoimmune diabetes in NOD female mice, which may be due to its inhibitory effect on the apoptosis of β cells.
出处
《中华内分泌代谢杂志》
CAS
CSCD
北大核心
2002年第5期380-383,共4页
Chinese Journal of Endocrinology and Metabolism
基金
国家自然科学基金资助项目 (3 9770 3 5 2 )
关键词
近交NOD
Freund佐剂
胰岛炎
脱噬作用
I型糖尿病
Mice, inbred NOD
Freund′s adjuvant
Insulitis
Diabetes mellitus, insulin dependent
Apoptosis
