Robertson S, Cameron N E, Cotter M A
Department of Biomedical Sciences, University of Aberdeen, UK.
Diabetologia. 1992 Dec;35(12):1113-7. doi: 10.1007/BF00401363.
Recent data suggests that reduced nerve blood flow is implicated in the aetiology of experimental diabetic neuropathy, which may be prevented by manipulations that reduce receptor-mediated vasoconstrictor activity. This investigation examines the effects of nifedipine, a voltage-sensitive calcium channel antagonist which has a direct vasodilatory effect on vessels, on nerve conduction, hypoxic resistance and capillary density in streptozotocin-induced diabetic rats. Treated and non-treated non-diabetic and diabetic groups were employed. Diabetes duration was 2 months. Treatment was preventive, groups received a nifedipine dietary supplement (40 mg.kg-1.day-1) for 2 months from the start of the study. Conduction was measured in sciatic motor branches supplying tibialis anterior and gastrocnemius muscles, and sensory saphenous nerve. Diabetes resulted in a 23-28% reduction in motor conduction velocity (p < 0.001), and a 15% deficit for sensory saphenous nerve (p < 0.001). In the nifedipine-treated diabetic group, motor and sensory conduction deficits were minimal compared with non-treated diabetes (p < 0.001). Nifedipine treatment had no significant effect on conduction velocity in non-diabetic rats. In vitro measurement of sciatic nerve hypoxic resistance revealed a 60% increase in the time taken for compound action potential amplitude to reach half its initial value with diabetes (p < 0.001). This was not significantly affected by nifedipine treatment. Experimental diabetes or nifedipine treatment did not significantly alter sciatic nerve endoneurial capillary density. We conclude that nifedipine, a vasodilator which acts directly on vascular smooth muscle, prevents nerve conduction deficits in experimental diabetes.
近期数据表明，神经血流量减少与实验性糖尿病神经病变的病因有关，而减少受体介导的血管收缩活性的操作可能会预防这种病变。本研究考察了硝苯地平（一种对血管有直接舒张作用的电压敏感性钙通道拮抗剂）对链脲佐菌素诱导的糖尿病大鼠神经传导、抗缺氧能力及毛细血管密度的影响。采用了经治疗和未经治疗的非糖尿病组及糖尿病组。糖尿病病程为2个月。治疗为预防性的，从研究开始，各实验组给予硝苯地平膳食补充剂（40mg·kg-1·天-1），持续2个月。在支配胫前肌和腓肠肌的坐骨运动支以及隐神经上测量神经传导。糖尿病导致运动传导速度降低23%-28%（p<0.001），隐神经感觉功能有15%的缺损（p<0.001）。在硝苯地平治疗的糖尿病组中，与未治疗的糖尿病组相比，运动和感觉传导缺损最小（p<0.001）。硝苯地平治疗对非糖尿病大鼠的传导速度无显著影响。坐骨神经抗缺氧能力的体外测量显示，糖尿病状态下复合动作电位幅度降至初始值一半所需的时间增加了60%（p<0.001）。这并未受到硝苯地平治疗的显著影响。实验性糖尿病或硝苯地平治疗均未显著改变坐骨神经内膜毛细血管密度。我们得出结论，直接作用于血管平滑肌的血管舒张剂硝苯地平可预防实验性糖尿病中的神经传导缺损。
