Thliveris J A, Begleiter A, Manchur D, Johnston J B
Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Canada.
Life Sci. 1997;61(3):283-91. doi: 10.1016/s0024-3205(97)00384-6.
We have previously reported that weekly administration of the adenosine deaminase inhibitor, 2'-deoxycoformycin (dCF), reduces the incidence of insulin-dependent diabetes mellitus (IDDM) in the BB Wistar rat, and this effect is likely due to immunosuppression by dCF. In the present study, we examined the effect of altering the dose and scheduling of dCF on prevention of IDDM in the BB rat. When rats were treated from day 25 of age with 2.5, 4, or 10 mg of dCF/kg/week, the percentage of diabetes-free animals at 120 days of age was 40, 60, and 80% respectively, compared with 10% for control animals, demonstrating increased protection against IDDM with increased dCF dose. Histological assessment of the pancreata from animals that became diabetic revealed a marked mononuclear infiltrate and a loss of positive staining for beta cell granules. In contrast, pancreata from animals that remained diabetes-free appeared normal. Protection against IDDM by dCF was time dependent and only occurred if treatments were initiated by day 30 of age. In addition, the protective effect persisted after drug withdrawal. Further studies are required to determine the optimum duration of therapy with dCF to prevent IDDM and to examine the immunological mechanism responsible for this effect.
我们之前曾报道，每周给予腺苷脱氨酶抑制剂2'-脱氧助间型霉素（dCF）可降低BB Wistar大鼠胰岛素依赖型糖尿病（IDDM）的发病率，这种效应可能是由于dCF的免疫抑制作用。在本研究中，我们研究了改变dCF的剂量和给药方案对预防BB大鼠IDDM的影响。当大鼠从25日龄开始接受2.5、4或10 mg dCF/kg/周的治疗时，120日龄时无糖尿病动物的百分比分别为40%、60%和80%，而对照动物为10%，这表明随着dCF剂量的增加，对IDDM的保护作用增强。对患糖尿病动物胰腺的组织学评估显示有明显的单核细胞浸润以及β细胞颗粒阳性染色缺失。相比之下，无糖尿病动物的胰腺外观正常。dCF对IDDM的保护作用具有时间依赖性，且仅在30日龄前开始治疗时才会出现。此外，停药后保护作用仍然存在。需要进一步研究以确定预防IDDM的dCF最佳治疗持续时间，并研究造成这种效应的免疫机制。
