Nagamatsu M, Nickander K K, Schmelzer J D, Raya A, Wittrock D A, Tritschler H, Low P A
Department of Neurology, Mayo Foundation, Rochester, Minnesota 55905, USA.
Diabetes Care. 1995 Aug;18(8):1160-7. doi: 10.2337/diacare.18.8.1160.
To determine whether lipoic acid (LA) will reduce oxidative stress in diabetic peripheral nerves and improve neuropathy.
We used the model of streptozotocin-induced diabetic neuropathy (SDN) and evaluated the efficacy of LA supplementation in improving nerve blood flow (NBF), electrophysiology, and indexes of oxidative stress in peripheral nerves affected by SDN, at 1 month after onset of diabetes and in age-matched control rats. LA, in doses of 20, 50, and 100 mg/kg, was administered intraperitoneally five times per week after onset of diabetes.
NBF in SDN was reduced by 50%; LA did not affect the NBF of normal nerves but improved that of SDN in a dose-dependent manner. After 1 month of treatment, LA-supplemented rats (100 mg/kg) exhibited normal NBF. The most sensitive and reliable indicator of oxidative stress was reduction in reduced glutathione, which was significantly reduced in streptozotocin-induced diabetic and alpha-tocopherol-deficient nerves; it was improved in a dose-dependent manner in LA-supplemented rats. The conduction velocity of the digital nerve was reduced in SDN and was significantly improved by LA.
These studies suggest that LA improves SDN, in significant part by reducing the effects of oxidative stress. The drug may have potential in the treatment of human diabetic neuropathy.
确定硫辛酸(LA)是否会减轻糖尿病周围神经病变中的氧化应激并改善神经病变。
我们使用链脲佐菌素诱导的糖尿病神经病变(SDN)模型,在糖尿病发病1个月后,对年龄匹配的对照大鼠和受SDN影响的周围神经的神经血流(NBF)、电生理学及氧化应激指标进行评估,以评价补充LA的疗效。糖尿病发病后,每周5次腹腔注射剂量为20、50和100mg/kg的LA。
SDN中的NBF降低了50%;LA对正常神经的NBF无影响,但以剂量依赖方式改善了SDN的NBF。治疗1个月后,补充LA的大鼠(100mg/kg)表现出正常的NBF。氧化应激最敏感和可靠的指标是还原型谷胱甘肽的减少,在链脲佐菌素诱导的糖尿病神经及α-生育酚缺乏的神经中显著降低;在补充LA的大鼠中,其以剂量依赖方式得到改善。SDN中趾神经的传导速度降低,LA使其显著改善。
这些研究表明,LA显著改善SDN,部分原因是减轻氧化应激的影响。该药物可能在治疗人类糖尿病神经病变方面具有潜力。