Cameron N E, Cotter M A, Archibald V, Dines K C, Maxfield E K
Department of Biomedical Sciences, University of Aberdeen, Scotland, UK.
Diabetologia. 1994 May;37(5):449-59. doi: 10.1007/s001250050131.
Increased oxygen free radical activity, coupled with reduced protection against oxidative stress, could play a role in the aetiology of neurovascular abnormalities in experimental diabetes mellitus. To test this hypothesis, non-diabetic and streptozotocin-diabetic rats were treated with the anti-oxidant probucol or the pro-oxidant primaquine. One-month diabetes caused 21.4% and 13.6% reduction in sciatic motor and saphenous sensory conduction velocity (p < 0.001). These deficits were prevented by probucol treatment (p < 0.001). After 1-month untreated diabetes, conduction velocity deficits were reversed by a further month of probucol treatment (p < 0.001). For non-diabetic rats, primaquine treatment caused a 12.9% reduction in motor conduction velocity (p < 0.001), which was prevented by probucol treatment (p < 0.001). Primaquine treatment did not affect diabetic rats. Sciatic nerve nutritive endoneurial blood flow, measured using microelectrode polarography and hydrogen clearance, was 48.0% reduced by 2-month diabetes (p < 0.001). This was completely prevented by probucol treatment (p < 0.001). Primaquine treatment did not affect blood flow in diabetic rats. However, in non-diabetic rats it caused a 30.0% reduction (p < 0.01) which was prevented by probucol treatment (p < 0.05). Sciatic endoneurial oxygen tensions were also measured by microelectrode polarography. Mean tension was 38.8% reduced by diabetes (p < 0.001). This was prevented by probucol treatment. Non-diabetic rats given primaquine treatment showed a 21.7% reduction in endoneurial oxygen tension (p < 0.01). The data suggest that vascular-mediated nerve dysfunction in diabetes depends on oxidative stress, and that similar effects in non-diabetic rats may be produced by pro-oxidant treatment. This provides evidence for the potentially important role of oxygen free radical activity in diabetic neuropathy.
氧自由基活性增加，再加上对抗氧化应激的保护作用降低，可能在实验性糖尿病神经血管异常的病因学中起作用。为了验证这一假设，对非糖尿病大鼠和链脲佐菌素诱导的糖尿病大鼠分别给予抗氧化剂普罗布考或促氧化剂伯氨喹治疗。糖尿病1个月导致坐骨神经运动和隐神经感觉传导速度分别降低21.4%和13.6%（p<0.001）。普罗布考治疗可预防这些缺陷（p<0.001）。未经治疗的糖尿病1个月后，再用1个月的普罗布考治疗可逆转传导速度缺陷（p<0.001）。对于非糖尿病大鼠，伯氨喹治疗导致运动传导速度降低12.9%（p<0.001），普罗布考治疗可预防此情况（p<0.001）。伯氨喹治疗对糖尿病大鼠无影响。使用微电极极谱法和氢清除法测量，糖尿病2个月使坐骨神经神经内膜营养性血流减少48.0%（p<0.001）。普罗布考治疗可完全预防此情况（p<0.001）。伯氨喹治疗对糖尿病大鼠的血流无影响。然而，在非糖尿病大鼠中，它导致血流减少30.0%（p<0.01），普罗布考治疗可预防此情况（p<0.05）。还通过微电极极谱法测量坐骨神经神经内膜氧张力。糖尿病使平均张力降低38.8%（p<0.001）。普罗布考治疗可预防此情况。给予伯氨喹治疗的非糖尿病大鼠神经内膜氧张力降低21.7%（p<0.01）。数据表明，糖尿病中血管介导的神经功能障碍取决于氧化应激，并且促氧化剂治疗可能在非糖尿病大鼠中产生类似作用。这为氧自由基活性在糖尿病神经病变中潜在的重要作用提供了证据。
