van Dam P S, van Asbeck B S, Bravenboer B, van Oirschot J F, Gispen W H, Marx J J
Department of Medical Pharmacology, Rudolf Magnus Institute for Neurosciences, Utrecht University, The Netherlands.
Free Radic Biol Med. 1998 Jan 1;24(1):18-26. doi: 10.1016/s0891-5849(97)00122-6.
Nerve dysfunction in diabetes is associated with increased oxidative stress. Vitamin E depletion also leads to enhanced presence of reactive oxygen species (ROS). We compared systemic and endoneurial ROS activity and nerve conduction in vitamin E-depleted control and streptozotocin-diabetic rats (CE- and DE-), and in normally fed control and diabetic animals (CE+ and DE+). Nerve conduction was reduced in both diabetic groups. Vitamin E depletion caused a small further nerve conduction deficit in the diabetic, but not in the control animals. The combination of vitamin E deficiency and streptozotocin-diabetes (group DE-) appeared to be lethal. In the remaining groups, an important rise in sciatic nerve malondialdehyde (MDA) was observed in the vitamin E-depleted control rats. In contrast, plasma MDA levels were elevated in group DE+ only, whereas hydrogen peroxide levels were increased in group CE-. Endoneurial total and oxidized glutathione and catalase were predominantly elevated in group DE+. These data show that nerve lipid peroxidation induced by vitamin E depletion does not lead to reduced nerve conduction or changes in antioxidant concentrations as observed in STZ-diabetes. The marked systemic changes in MDA and antioxidants suggest that nerve dysfunction in experimental hyperglycemia is rather a consequence of systemic than direct nerve damage.
糖尿病中的神经功能障碍与氧化应激增加有关。维生素E缺乏也会导致活性氧（ROS）的存在增加。我们比较了维生素E缺乏的对照大鼠和链脲佐菌素诱导的糖尿病大鼠（CE-和DE-）以及正常喂养的对照和糖尿病动物（CE+和DE+）的全身和神经内膜ROS活性及神经传导情况。两个糖尿病组的神经传导均降低。维生素E缺乏在糖尿病动物中进一步导致了轻微的神经传导缺陷，但在对照动物中未出现。维生素E缺乏与链脲佐菌素诱导的糖尿病相结合（DE-组）似乎是致命的。在其余组中，维生素E缺乏的对照大鼠坐骨神经丙二醛（MDA）显著升高。相比之下，仅DE+组血浆MDA水平升高，而CE-组过氧化氢水平升高。DE+组神经内膜总谷胱甘肽、氧化型谷胱甘肽和过氧化氢酶主要升高。这些数据表明，维生素E缺乏诱导的神经脂质过氧化不会像在链脲佐菌素诱导的糖尿病中那样导致神经传导降低或抗氧化剂浓度改变。MDA和抗氧化剂的显著全身变化表明，实验性高血糖中的神经功能障碍更多是全身因素而非直接神经损伤的结果。
