Malone J I, Lowitt S, Salem A F, Miranda C, Korthals J K, Carver J
Diabetes Center and the Department of Pediatrics, University of South Florida, Tampa, FL 33612-4799, USA.
Metabolism. 1996 Jul;45(7):902-7. doi: 10.1016/s0026-0495(96)90167-5.
Nerve conduction velocity (NCV) increased with age in nondiabetic male Wistar rats for the first 26 weeks of life. The NCV of animals made hyperglycemic at age 6 weeks by administration of streptozotocin (STZ) also increases, but at a slower rate. Animals with 4 weeks of hyperglycemia and reduced NCV treated with an aldose reductase inhibitor (sorbinil) or a short-chain acyl-carnitine (acetyl-L-carnitine [ALC]) daily for 16 weeks showed an improvement in NCV. Morphometric studies of tibial nerves collected from animals after 20 weeks of hyperglycemia (age 26 weeks) showed a consistent reduction in the width of the myelin sheath and little change in axon area. The number of large myelinated fibers (>6.5 microns) found in nerves collected from hyperglycemic animals was less than the number found in nondiabetic animals. Treatment of hyperglycemic rats with either sorbinil or ALC was associated with increased NCV, myelin width, and large myelinated fibers. The apparent metabolic effect of these agents was similar for fatty acid metabolism, but different for polyol pathway activity. We conclude that in animals hyperglycemic long enough to slow NCV, sorbinil and/or ALC treatment reduces the functional, structural, and biochemical changes associated with hyperglycemia that occur in the myelin sheath.
在非糖尿病雄性Wistar大鼠出生后的前26周，神经传导速度（NCV）随年龄增长而增加。通过注射链脲佐菌素（STZ）在6周龄时造成高血糖的动物，其NCV也会增加，但速度较慢。对高血糖4周且NCV降低的动物，每天给予醛糖还原酶抑制剂（索比尼尔）或短链酰基肉碱（乙酰-L-肉碱[ALC]），持续16周，结果显示NCV有所改善。对高血糖20周（26周龄）的动物采集的胫神经进行形态计量学研究，结果显示髓鞘宽度持续减小，轴突面积变化不大。从高血糖动物采集的神经中发现的大髓鞘纤维（>6.5微米）数量少于非糖尿病动物。用索比尼尔或ALC治疗高血糖大鼠，可使NCV、髓鞘宽度和大髓鞘纤维数量增加。这些药物对脂肪酸代谢的表观代谢作用相似，但对多元醇途径活性的作用不同。我们得出结论，在高血糖时间足够长以至于NCV减慢的动物中，索比尼尔和/或ALC治疗可减少与高血糖相关的、发生在髓鞘中的功能、结构和生化变化。
