Miyauchi Y, Shikama H, Takasu T, Okamiya H, Umeda M, Hirasaki E, Ohhata I, Nakayama H, Nakagawa S
Endocrinology and Metabolic Disease Research Laboratory, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Japan.
Eur J Endocrinol. 1996 Apr;134(4):467-73. doi: 10.1530/eje.0.1340467.
The aims of this study were to investigate the effect of aminoguanidine (AG) on slowing of motor nerve conduction velocity (MNCV) of the sciatic nerve in streptozocin-induced diabetic rats and to assess its mechanism of action. The MNCV of the sciatic nerve was measured electrophysiologically in diabetic rats treated with and without AG for 16 weeks. To elucidate the action of AG, morphological lesion and abnormality of polyol pathway metabolism in the nerve were examined and tissue levels of advanced glycosylation end-products (AGE) were determined as an indicator of AGE accumulation in tissue. Diabetic rats were treated with AG at three doses of 10, 25 and 50 mg/kg for 16 weeks. Myelinated fiber morphometry and nerve Na+,K(-)-ATPase activity were determined. The AGE levels in renal cortex were measured by a specific ELISA. Aminoguanidine dose-dependently ameliorated slowing of MNCV 16 weeks after the treatment without changing body weight or blood glucose levels. No difference in myelinated fiber morphometry or Na+,K(+)-ATPase activity with or without AG treatment was detected in diabetic rats. Diabetes increased the AGE level in the renal cortex by six times compared to non-diabetic rats, and AG reduced the rise in the AGE level by 40%. The MNCV was inversely correlated with the AGE levels. We conclude that improvement of conduction slowing by AG in experimental diabetes may be through decreasing the AGE level in the peripheral tissues. Aminoguanidine may have a therapeutic potential in controlling diabetic peripheral neuropathy.
本研究的目的是探讨氨基胍（AG）对链脲佐菌素诱导的糖尿病大鼠坐骨神经运动神经传导速度（MNCV）减慢的影响，并评估其作用机制。对接受和未接受AG治疗16周的糖尿病大鼠进行坐骨神经MNCV的电生理测量。为阐明AG的作用，检测了神经中的形态学损伤和多元醇途径代谢异常，并测定了晚期糖基化终产物（AGE）的组织水平，作为组织中AGE积累的指标。糖尿病大鼠分别接受10、25和50mg/kg三种剂量的AG治疗16周。测定有髓纤维形态学和神经钠钾ATP酶活性。用特异性酶联免疫吸附测定法（ELISA）测量肾皮质中的AGE水平。治疗16周后，氨基胍剂量依赖性地改善了MNCV减慢，且未改变体重或血糖水平。在糖尿病大鼠中，未检测到AG治疗组与未治疗组在有髓纤维形态学或钠钾ATP酶活性方面的差异。与非糖尿病大鼠相比，糖尿病使肾皮质中的AGE水平增加了6倍，而AG使AGE水平的升高降低了40%。MNCV与AGE水平呈负相关。我们得出结论，AG改善实验性糖尿病中神经传导减慢可能是通过降低外周组织中的AGE水平实现的。氨基胍在控制糖尿病周围神经病变方面可能具有治疗潜力。
