Cameron N E, Dines K C, Cotter M A
Department of Biomedical Sciences, University of Aberdeen, Scotland, UK.
Diabetologia. 1994 Dec;37(12):1209-15. doi: 10.1007/BF00399794.
Abnormal vascular endothelium function may contribute to the reduced nerve perfusion implicated in the aetiology of neuropathy in diabetes mellitus. The aim was to test the hypothesis that a powerful vasoconstrictor, endothelin-1, could be involved in nerve dysfunction in streptozotocin-diabetic rats. After 6 weeks of untreated diabetes, rats were implanted with osmotic minipumps which continuously delivered the endothelin-1 antagonist, BQ-123, to the circulation via a jugular vein cannula. Sciatic motor conduction velocity, monitored serially, was increased after 4 days, treatment (p = 0.028), and reached asymptote by 9-11 days (p = 0.0001), when the degree of amelioration was approximately 60% of the initial diabetic deficit. Treatment of non-diabetic rats for 13 days with BQ-123 had no significant effect on motor conduction velocity. Sensory saphenous nerve conduction velocity was measured acutely after 20 days, BQ-123 treatment. The amelioration of a sensory deficit was approximately 80% (p < 0.001); the resultant conduction velocity value was not significantly different from that of a non-diabetic control group. After 20 days, treatment, sciatic nutritive endoneurial blood flow was measured by microelectrode polarography and hydrogen clearance. A 48% deficit with untreated diabetes (p < 0.001) was 64% ameliorated by BQ-123 treatment (p < 0.001). In non-diabetic rats, BQ-123 treatment had no effect on blood flow. We conclude that endothelin-1 does not seem to be involved in the control of nerve blood flow in non-diabetic rats; however, it makes a major contribution to the perfusion deficit in experimental diabetes. This has deleterious consequences for nerve conduction, and it is possible that endothelin-1 receptor blockade may have therapeutic potential in diabetic patients.
异常的血管内皮功能可能导致神经灌注减少，这与糖尿病性神经病变的病因有关。本研究旨在验证一种强效血管收缩剂——内皮素-1是否参与链脲佐菌素诱导的糖尿病大鼠的神经功能障碍。未经治疗的糖尿病持续6周后，通过颈静脉插管将渗透微型泵植入大鼠体内，使其持续向循环系统输送内皮素-1拮抗剂BQ-123。连续监测坐骨神经运动传导速度，治疗4天后增加（p = 0.028），9 - 11天达到稳定状态（p = 0.0001），改善程度约为糖尿病初始缺损的60%。用BQ-123治疗非糖尿病大鼠13天，对运动传导速度无显著影响。BQ-123治疗20天后，急性测量隐神经感觉传导速度。感觉功能缺损的改善程度约为80%（p < 0.001）；最终传导速度值与非糖尿病对照组无显著差异。治疗20天后，通过微电极极谱法和氢清除法测量坐骨神经营养性神经内膜血流。未治疗的糖尿病大鼠血流缺损48%（p < 0.001），BQ-123治疗后改善6�%（p < 0.001）。在非糖尿病大鼠中，BQ-123治疗对血流无影响。我们得出结论，内皮素-1似乎不参与非糖尿病大鼠神经血流的调控；然而，它在实验性糖尿病的灌注缺损中起主要作用。这对神经传导有有害影响，内皮素-1受体阻断可能对糖尿病患者具有治疗潜力。
