Therapeutic effects of aldose reductase inhibitor on experimental diabetic neuropathy through synthesis/secretion of nerve growth factor

被引:46
|
作者
Ohi, T
Saita, K
Furukawa, S
Ohta, M
Hayashi, K
Matsukura, S
机构
[1] Miyazaki Med Coll, Dept Internal Med 1, Div Neurol, Kiyotake, Miyazaki 88916, Japan
[2] Gifu Pharmaceut Univ, Dept Biol Mol, Gifu, Japan
[3] Natl Utano Hosp, Clin Res Ctr, Kyoto, Japan
关键词
NGF; CNTF; aldose reductase inhibitor; diabetic neuropathy; Schwann cell culture;
D O I
10.1006/exnr.1998.6821
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
We investigated alterations in nerve growth factor (NGF) and ciliary neurotrophic factor (CNTF) contents during treatment with epalrestat, an aldose reductase inhibitor (ARI), on streptozotocin (STZ)induced diabetic neuropathy in rats. Diabetic rats showed a statistically significant reduction in H-wave-related sensory nerve conduction velocity (HSNCV) and in NGF content in sciatic nerves during the experiment of 8 weeks. No reduction in the CNTF content in sciatic nerves was seen in the diabetic rats. The epalrestat treatment, which started 4 weeks after STZ injection, resulted in a significantly greater NGF content and faster HSNCV than those in untreated diabetic rats. But no statistically significant alterations of motor nerve conduction velocity (MNCV) or CNTF content were seen during the treatment. ARI showed the stimulating effect for NGF synthesis/secretion in rat Schwann cell culture in vitro. These findings suggest that decreased levels of NGF in diabetic sciatic nerves may be involved in the pathogenesis of diabetic neuropathy in these rats and further show that epalrestat treatment can be useful for the treatment of diabetic neuropathy through NGF-induction in Schwann cells and/or inhibition of the polyol pathway. (C) 1998 Academic Press.
引用
收藏
页码:215 / 220
页数:6
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