Ford I, Cotter M A, Cameron N E, Greaves M
Departments of Medicine & Therapeutics, University of Aberdeen, Aberdeen, Scotland.
Metabolism. 2001 Aug;50(8):868-75. doi: 10.1053/meta.2001.24914.
Oxidative stress and defective fatty acid metabolism in diabetes may lead to impaired nerve perfusion and contribute to the development of peripheral neuropathy. We studied the effects of 2-week treatments with evening primrose oil (EPO; n = 16) or the antioxidant alpha-lipoic acid (ALA; n = 16) on endoneurial blood flow, nerve conduction parameters, lipids, coagulation, and endothelial factors, in rats with streptozotocin-induced diabetes. Compared with their nondiabetic littermates, untreated diabetic rats had impaired sciatic motor and saphenous sensory nerve-conduction velocity (NCV; P <.001), reduced endoneurial blood flow (P <.001), and increased serum triglycerides (P <.01), cholesterol (P < 0.01), plasma factor VII (P <.0001), and von Willebrand factor (vWF; P <.0001). Plasma fibrinogen and serum high-density lipoprotein concentrations were not significantly different. Treatment with either ALA or EPO effectively corrected the deficits in NCV and endoneurial blood flow. ALA was associated with marked and statistically significant decreases in fibrinogen, factor VII, vWF, and triglycerides (P <.01, paired t tests before v after treatment). In contrast, EPO was associated with significant (P <.05) increases in fibrinogen, factor VII, vWF, triglycerides, and cholesterol and a significant decrease in high-density lipoprotein. Changes in levels of coagulation factors and lipids, qualitatively similar to those found with EPO, were obtained with a diet containing sunflower oil (to control for calorific and lipid content) or with a normal diet alone. Blood glucose and hematocrit levels were not significantly altered by treatments. These data suggest that although both ALA and EPO improve blood flow and nerve function, their actions on vascular factors differ. The marked effects of ALA in lowering lipid and hemostatic risk factors for cardiovascular disease indicate potential antithrombotic and antiatherosclerotic actions that could be of benefit in human diabetes and merit further study.
糖尿病中的氧化应激和脂肪酸代谢缺陷可能导致神经灌注受损，并促使周围神经病变的发展。我们研究了用月见草油（EPO；n = 16）或抗氧化剂α-硫辛酸（ALA；n = 16）对链脲佐菌素诱导的糖尿病大鼠进行为期2周的治疗，对神经内膜血流、神经传导参数、脂质、凝血和内皮因子的影响。与非糖尿病同窝仔鼠相比，未经治疗的糖尿病大鼠坐骨神经运动和隐神经感觉神经传导速度（NCV）受损（P <.001），神经内膜血流减少（P <.001），血清甘油三酯升高（P <.01）、胆固醇（P < 0.01）、血浆因子VII（P <.0001）和血管性血友病因子（vWF；P <.0001）。血浆纤维蛋白原和血清高密度脂蛋白浓度无显著差异。用ALA或EPO治疗可有效纠正NCV和神经内膜血流的缺陷。ALA与纤维蛋白原、因子VII、vWF和甘油三酯的显著且具有统计学意义的降低有关（P <.01，治疗前后配对t检验）。相比之下，EPO与纤维蛋白原、因子VII、vWF、甘油三酯和胆固醇的显著升高（P <.05）以及高密度脂蛋白的显著降低有关。用含向日葵油的饮食（以控制热量和脂质含量）或单独用正常饮食也得到了与EPO类似的凝血因子和脂质水平的定性变化。治疗后血糖和血细胞比容水平无显著改变。这些数据表明，虽然ALA和EPO都能改善血流和神经功能，但它们对血管因子的作用不同。ALA在降低心血管疾病的脂质和止血危险因素方面的显著作用表明其潜在的抗血栓形成和抗动脉粥样硬化作用，这可能对人类糖尿病有益，值得进一步研究。
