van Dam P S, van Asbeck B S, Van Oirschot J F, Biessels G J, Hamers F P, Marx J J
University Medical Center, Utrecht, The Netherlands.
Eur J Clin Invest. 2001 May;31(5):417-24. doi: 10.1046/j.1365-2362.2001.00832.x.
Increased oxidative stress is considered to be a causal factor in the development of diabetic complications, among which peripheral neuropathy. The pathophysiology of nerve dysfunction in diabetes has been explained both by reduced endoneurial microcirculation and alterations in endoneurial metabolism. It is unclear whether antioxidants primarily improve nerve blood flow or normalise systemic or endoneurial oxidative metabolism. Therefore, we evaluated the effects of the antioxidants glutathione and alpha-lipoic acid on both nerve microcirculation and the antioxidative capacity and lipid peroxidation in experimentally diabetic rats.
Streptozotocin-diabetic rats were treated with different doses of alpha-lipoic acid, reduced glutathione or placebo, and were compared with nondiabetic controls. We measured systemic and endoneurial antioxidants, malondialdehyde and whole blood hydrogen peroxide. Furthermore, we evaluated sciatic and tibial motor and sensory nerve conduction velocity, caudal nerve conduction velocity, and assessed sciatic nerve blood flow and vascular resistance by Laser-Doppler flowmetry.
We observed a rise in erythrocyte glutathione by 27 % (P < 0.05), and a trend towards decreased plasma malondialdehyde in alpha-lipoic acid, but not in glutathione-treated animals in comparison with the placebo group. Simultaneously, sciatic nerve blood flow and vascular resistance were improved by daily alpha-lipoic acid administration by 38% (P < 0.05). Peripheral nerve conduction velocity and endoneurial glutathione were not significantly influenced by antioxidant treatment.
Only minor beneficial effects of alpha-lipoic acid on nerve blood flow and oxidative state occur at the given doses; these effects were insufficient to improve nerve conduction deficits.
氧化应激增加被认为是糖尿病并发症（包括周围神经病变）发生发展的一个致病因素。糖尿病神经功能障碍的病理生理学已通过神经内膜微循环减少和神经内膜代谢改变来解释。目前尚不清楚抗氧化剂主要是改善神经血流还是使全身或神经内膜氧化代谢正常化。因此，我们评估了抗氧化剂谷胱甘肽和α-硫辛酸对实验性糖尿病大鼠神经微循环、抗氧化能力及脂质过氧化的影响。
用不同剂量的α-硫辛酸、还原型谷胱甘肽或安慰剂治疗链脲佐菌素诱导的糖尿病大鼠，并与非糖尿病对照组进行比较。我们测量了全身和神经内膜抗氧化剂、丙二醛和全血过氧化氢。此外，我们评估了坐骨神经和胫神经的运动及感觉神经传导速度、尾神经传导速度，并通过激光多普勒血流仪评估了坐骨神经血流和血管阻力。
与安慰剂组相比，我们观察到α-硫辛酸治疗组红细胞谷胱甘肽升高了27%（P<0.05），血浆丙二醛有降低趋势，但谷胱甘肽治疗组无此现象。同时，每日给予α-硫辛酸可使坐骨神经血流和血管阻力改善38%（P<0.05）。抗氧化剂治疗对周围神经传导速度和神经内膜谷胱甘肽无显著影响。
在给定剂量下，α-硫辛酸对神经血流和氧化状态仅有轻微的有益作用；这些作用不足以改善神经传导缺陷。
