Ohi T, Saita K, Furukawa S, Ohta M, Hayashi K, Matsukura S
Division of Neurology, Department of Internal Medicine, Miyazaki Medical College, 5200 Kihara, Kiyotake-cho, Miyazaki, 889-16, Japan.
Exp Neurol. 1998 Jun;151(2):215-20. doi: 10.1006/exnr.1998.6821.
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.
我们研究了在大鼠中，用醛糖还原酶抑制剂（ARI）依帕司他治疗链脲佐菌素（STZ）诱导的糖尿病性神经病变期间，神经生长因子（NGF）和睫状神经营养因子（CNTF）含量的变化。在8周的实验期间，糖尿病大鼠的H波相关感觉神经传导速度（HSNCV）和坐骨神经中NGF含量出现了具有统计学意义的降低。糖尿病大鼠坐骨神经中的CNTF含量未见降低。在STZ注射4周后开始的依帕司他治疗，导致与未治疗的糖尿病大鼠相比，NGF含量显著更高，HSNCV更快。但在治疗期间，运动神经传导速度（MNCV）或CNTF含量未见具有统计学意义的变化。ARI在体外大鼠雪旺细胞培养中显示出对NGF合成/分泌的刺激作用。这些发现表明，糖尿病坐骨神经中NGF水平降低可能参与了这些大鼠糖尿病性神经病变的发病机制，并进一步表明依帕司他治疗可通过诱导雪旺细胞中的NGF和/或抑制多元醇途径用于治疗糖尿病性神经病变。
