霍乱毒素B亚单位-胰岛素原融合蛋白抗糖尿病

高玲; 张大兵; 任宏; 欧阳凤秀; 姜庆五

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

摘要

摘要:
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 40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)500 μl, 胰岛素(insulin)1mg, CTB--proinsulin 100 μg+CTG五聚体1μg, CTB^--proinsulin 300 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26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, 26周龄时小鼠糖尿病的累积发病率: PBS组100%, CTB-proinsulin 100 μg+CTG五聚体1μg组、CTG-proinsulin 300 μg+CTG五聚体3μg组和胰岛素组分别为40%, 40%和50%(P < 0.010)。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。

Abstract:
Objective To observe the diabetes prevention effects of oral administration of human insulin and admixtures of proinsulin coupled to cholera toxin B subunit(CTB)and CTB(CTB-proinsulin+CTB)on female non-obese diabetic mice.
Methods 40 female NOD mice were divided randomly into four groups.Group1:PBS 500Ll, group 2:insulin, group 3:CTBproinsulin 100μg+CTB 1μg, group 4:CTB-proinsulin 300 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-proinsulin+CTB to female NOD mice significantly suppressed incidence of diabetes.The cumulative incidence of PBS, insulin, CTB-proinsulin 100μg+CTB 1 μg, CTB-proinsulin 300 μg+CTB 3 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 lower than that of insulin at the same prevention rate.

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