谷氨酸脱羧酶通过调节T细胞亚群预防NOD小鼠发生1型糖尿病

　　关键词： 谷氨酸脱羧酶；小鼠，近交NOD；糖尿病，胰 岛素依赖型；T淋巴细胞亚群

　　【摘要】　目的　 了解谷氨酸脱羧酶(GAD)对非肥胖糖尿病(NOD)小鼠的1型糖尿病是否具有预防作用并探讨其 免 疫作用机制。方法　用猪脑GAD和不完全弗氏佐剂(FIA )混合后给4周龄雌性NOD小鼠腹腔注射(32例)，同时单独注射等量FIA作为对照组。8周龄时 腹腔注射环磷酰胺以加速糖尿病。每周测定体重、血糖，糖尿病形成2周或20周龄处死小鼠 后测定血清C-肽、GAD抗体(GAD-Ab)和脾组织T细胞亚群，观察胰腺病理、免疫组化和超微 结构变化。结果　20周龄时，FIA对照组的糖尿病总发 病率为73.68%，而GAD组仅为6.25%(P＜0.01 )，发病时 间也明显延缓；GAD组的胰岛炎症分数较FIA组明显降低，且炎症程度减轻(P＜0.05)；GAD组的C-肽水平也明显高于对照组(P＜0.05)；两组的GAD-Ab阳性率无明显差别 ；FIA组的脾脏T细胞以CD+4亚群为主，GAD组则CD+8亚群比例增高，CD4/CD8比 值显著下降(P＜0.01)；免疫组化也表明FIA组胰岛浸润淋巴 细胞为CD+4T细胞，而GAD组胰岛CD+4细胞明显减少，且局限于胰周。结论　猪脑GAD有预防NOD小鼠胰岛炎和糖尿病发生的作用，其机制 可能与改善小鼠缺陷的CD+8T细胞亚群有关。

Glutamic acid decarboxylase prevents type 1 diabetes by regulating the subsets of T lymphocytes in NOD mice

LI U Fang　YU Maohua　ZHU Qiuyu　et al

　　（Department of Endocrinology,Huashan Hospital ,Shanghai medical University,Shanghai 200040）

　　【Abstract】　Objective　To observe whether glutamic acid decarboxylase (GAD) can prevent type 1 diab etes in nonobese diabetic (NOD) mice and to study its influence on the immune sy stem. Methods　One injection was performed intra peritoneally (i.p.) with GAD purified from pig brain, together with Freund incom plete adjuvents (FIA), into female NOD mice at the age of 4 weeks as treated gro up (n=32), other 19 mice were injected FIA 100 μl alone as control group. Diabetes was accelerated 4 weeks later by a single injection of cyclophosphamide. Blood glucose and body weight were me asured weekly. At the age of 20 weeks or 2 weeks after the onset of diabetes, mi ce in two groups were killed and the serum levels of C-peptide and an tibodies against GAD were detected with radioimmunoassay and ELISA respectively. The subsets of T cells in spleen were determined by two-color FACS analysis, t he ultrastructure of β cells was observed, and pancreatic histopathological and immunocytochemical studies were performed using the anti-CD4 or anti-CD8 monoclonal antibodies. Results　Immunization wit h GAD reduced the incidence of diabet

[1] [2] [3] [4] [5] [6] 下一页