Shimoshige Y, Ikuma K, Yamamoto T, Takakura S, Kawamura I, Seki J, Mutoh S, Goto T
Department of Metabolic Diseases, Fujisawa Pharmaceutical, Osaka, Japan.
Metabolism. 2000 Nov;49(11):1395-9. doi: 10.1053/meta.2000.17723.
We studied the effects of zenarestat, an aldose reductase inhibitor (ARI), on peripheral neuropathy in Zucker diabetic fatty (ZDF) rats, an animal model of type 2 diabetes. ZDF rats and their lean rats counterparts were fed a sucrose-containing diet, and zenarestat was given orally once a day for 8 weeks. Motor nerve conduction velocity (MNCV), F-wave minimal latency (FML), and sorbitol concentrations in the sciatic nerve were measured. In ZDF control rats, a remarkable accumulation of sorbitol, a delay in FML, and a slowing of MNCV were observed compared with lean rats. At a dose of 3.2 mg/kg, zenarestat had no significant effect on the delay in FML and the slowing of MNCV, although the sorbitol accumulation in the sciatic nerve was partially inhibited in ZDF rats. On the other hand, 32 mg/kg zenarestat treatment improved these nerve dysfunctions in ZDF rats, along with a reduction of nerve sorbitol accumulation almost to the level of lean rats. These data showed that zenarestat improved diabetic peripheral neuropathy in ZDF rats, a type 2 diabetes model, providing evidence for the therapeutic potential of zenarestat for the treatment of diabetic neuropathy.
我们研究了醛糖还原酶抑制剂（ARI）泽那司他对2型糖尿病动物模型——Zucker糖尿病脂肪（ZDF）大鼠周围神经病变的影响。给ZDF大鼠及其瘦型对照大鼠喂食含蔗糖的饮食，并每天口服一次泽那司他，持续8周。测量运动神经传导速度（MNCV）、F波最小潜伏期（FML）以及坐骨神经中的山梨醇浓度。与瘦型大鼠相比，在ZDF对照大鼠中观察到山梨醇显著蓄积、FML延迟以及MNCV减慢。在3.2mg/kg的剂量下，尽管泽那司他部分抑制了ZDF大鼠坐骨神经中的山梨醇蓄积，但对FML延迟和MNCV减慢没有显著影响。另一方面，32mg/kg泽那司他治疗改善了ZDF大鼠的这些神经功能障碍，同时神经山梨醇蓄积减少至几乎与瘦型大鼠相同的水平。这些数据表明，泽那司他改善了2型糖尿病模型ZDF大鼠的糖尿病周围神经病变，为泽那司他治疗糖尿病神经病变的潜在治疗作用提供了证据。
