van der Sloot P, Mizisin A, Zochodne D
Department of Clinical Neurosciences, University of Calgary, Alberta, Canada.
Can J Neurol Sci. 1995 Aug;22(3):198-201. doi: 10.1017/s0317167100039846.
In two previous studies we have demonstrated prevention of electrophysiological abnormalities of nerve in experimental STZ (streptozotocin)-induced diabetes (ED) of rats using nonsteroidal anti-inflammatory agents: indomethacin and sulindac. Sulindac might benefit ED because it inhibits both cyclo-oxygenase and aldose reductase.
In this work, we examined whether 1 month of sulindac treatment reversed or improved established biochemical and electrophysiological abnormalities in experimental diabetes of 3 months duration. Sulindac-treated diabetic rats (6.0 mg/kg 5/7 days weekly by gavage) were compared to untreated diabetics, nondiabetic controls and sulindac treated control rats.
Diabetic rats developed slowing of conduction velocity in caudal sensory, sural sensory, caudal motor and sciatic tibial motor fibers. Sulindac improved caudal motor and, to a lesser extent sural sensory conduction but not caudal sensory or sciatic tibial motor conduction. Sulindac did not alter sciatic sugars or polyols.
Sulindac provided modest improvement in some indices of experimental neuropathy in this reversal study, but there was less efficacy than in the preventative study. Reversal paradigms should be examined in all experimental therapies for diabetic neuropathy.
在之前的两项研究中,我们已证明使用非甾体抗炎药吲哚美辛和舒林酸可预防实验性链脲佐菌素(STZ)诱导的大鼠糖尿病(ED)中神经的电生理异常。舒林酸可能对ED有益,因为它可同时抑制环氧化酶和醛糖还原酶。
在本研究中,我们检测了舒林酸治疗1个月是否能逆转或改善已持续3个月的实验性糖尿病中已出现的生化和电生理异常。将经舒林酸治疗的糖尿病大鼠(每周5/7天,通过灌胃给予6.0mg/kg)与未治疗的糖尿病大鼠、非糖尿病对照大鼠以及经舒林酸治疗的对照大鼠进行比较。
糖尿病大鼠的尾侧感觉、腓肠感觉、尾侧运动和坐骨神经胫侧运动纤维的传导速度减慢。舒林酸改善了尾侧运动以及在较小程度上改善了腓肠感觉传导,但未改善尾侧感觉或坐骨神经胫侧运动传导。舒林酸未改变坐骨神经中的糖或多元醇。
在这项逆转研究中,舒林酸使实验性神经病变的某些指标有适度改善,但疗效低于预防性研究。对于糖尿病神经病变的所有实验性治疗,都应检验逆转模式。