Hotta N, Koh N, Sakakibara F, Nakamura J, Hamada Y, Hara T, Mori K, Naruse K, Fukasawa H, Kakuta H, Sakamoto N
Third Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Eur J Pharmacol. 1996 Oct 17;313(3):201-9. doi: 10.1016/0014-2999(96)00512-2.
To investigate the pathogenesis of diabetic neuropathy in non-insulin-dependent diabetes mellitus, Otsuka Long-Evans Tokushima Fatty rats, an animal model of non-insulin-dependent diabetes mellitus, and non-diabetic Long-Evans Tokushima Otsuka rats were fed with or without sucrose and/or cilostazol, an anticoagulant, for 8 weeks. Sucrose-fed diabetic rats showed a delayed motor nerve conduction velocity, decreased R-R interval variability of electrocardiogram, reduced sciatic nerve blood flow, increased platelet aggregability and a decreased erythrocyte 2,3-diphosphoglycerate concentration compared with non-sucrose-fed diabetic rats and non-diabetic rats. These abnormalities were significantly prevented by treatment with cilostazol without changes in the nerve tissue levels of polyols. These findings indicate that sucrose-fed Otsuka Long-Evans Tokushima Fatty rats may be a useful animal model of neuropathy in non-insulin-dependent diabetes mellitus, and that cilostazol may prevent the development of diabetic neuropathy by modifying vascular factors.
为研究非胰岛素依赖型糖尿病中糖尿病神经病变的发病机制,将非胰岛素依赖型糖尿病动物模型大冢长- Evans德岛肥胖大鼠和非糖尿病的大冢长- Evans德岛大鼠分别给予或不给予蔗糖和/或抗凝血剂西洛他唑喂养8周。与未喂蔗糖的糖尿病大鼠和非糖尿病大鼠相比,喂蔗糖的糖尿病大鼠表现出运动神经传导速度延迟、心电图R-R间期变异性降低、坐骨神经血流量减少、血小板聚集性增加以及红细胞2,3 -二磷酸甘油酸浓度降低。用西洛他唑治疗可显著预防这些异常,而神经组织中多元醇水平无变化。这些发现表明,喂蔗糖的大冢长- Evans德岛肥胖大鼠可能是研究非胰岛素依赖型糖尿病神经病变的有用动物模型,且西洛他唑可能通过改变血管因素来预防糖尿病神经病变的发展。