霍乱毒素B亚单位-胰岛素原融合蛋白抗糖尿病

Effect of cholera toxoid-proinsulin conjugate and cholera toxin B sub unit admixtures on spontaneous autoimmune diabetes

目的 观察雌性非肥胖糖尿病(NOD)小鼠口服胰岛素和霍乱毒素B亚单位 胰岛素原融合蛋白(CTB proinsulin) +霍乱毒素B亚单位五聚体(CTB五聚体)对糖尿病发生的影响,为社区非肥胖性糖尿病干预提供参考依据。方法 4 0只雌性3～4周龄NOD小鼠随机分为4组:分别给予磷酸缓冲液(PBS) 5 0 0 μl,胰岛素(insulin) 1mg ,CTB - proinsulin 10 0 μg +CTG五聚体1μg ,CTB - proinsulin 30 0 μg +CTG五聚体3μg。每周灌胃2次至12周龄;从12周龄起,动态监测小鼠尿糖、血糖至2 6周龄,观察糖尿病的发生,比较不同抗原诱导免疫耐受的作用。结果 与PBS组比较,CTB proinsulin +CTG五聚体与胰岛素均能延缓、减少NOD小鼠糖尿病的发生,2 6周龄时小鼠糖尿病的累积发病率:PBS组10 0 % ,CTB proinsulin 10 0 μg +CTG五聚体1μg组、CTG proinsulin 30 0 μg +CTG五聚体3μg组和胰岛素组分别为4 0 % ,4 0 %和5 0 % (P <0 .0 10 )。各组生存时间分布有差别。结论 不同剂量组的CTB proinsulin +CTG五聚体与胰岛素能够提高NOD鼠生存率,并可达到与胰岛素相同保护作用而所需抗原剂量较小。

Objective To observe the diabetes prevention effects of o ral administration of human insulin and admixtures of proinsulin coupled to chol era toxin B subunit(CTB) and CTB (CTB-proinsulin+CTB)on female non-obese diabe tic mice.Methods 40 female NOD mice were divided randomly into fou r groups.Group1:PBS 500μl,group 2:insulin, group 3:CTB-proinsulin100μg+CTB1 ?μg,group 4:CTB-proinsulin300?μg+CTB3?μg.The whole observation lasted 26 months. Glycosuria and glycemia were measured from 11 weeks to 26 weeks. Results Oral administration of insulin and CTB-proinsuli n+CTB to female NOD mice significantly suppressed incidence of diabetes. The cum ulative incidence of PBS,insulin,CTB-proinsulin100?μg+CTB1?μg,CTB-proinsul in300?μg+CTB3?μg were 100%,40%,40%,50% (P<0.010)respectively.Survival distribuding were all significantly difference. Conclusion The needed dose of CTB-proinsulin+CTB is lowe r than that of insulin at the same prevention rate.