Forcier N J, Mizisin A P, Rimmer M A, Powell H C
Department of Pathology (Neuropathology), University of California, San Diego, La Jolla 92093.
J Neuropathol Exp Neurol. 1991 May;50(3):235-55. doi: 10.1097/00005072-199105000-00006.
The effect of chronic hyperglycemia and polyol pathway activation on the Schwann cell has not been resolved although injury to this cell has long been suspected in diabetic neuropathy. Hyperglycemia, resulting from galactose intoxication of four months duration, induces dose-dependent accumulations of endoneurial fluid sodium and chloride that are linked to polyol pathway activity and associated with dose-dependent increases in sciatic nerve water content, endoneurial fluid pressure and (Na+, K+)-ATPase activity. In order to understand the impact of these changes on the nerve microenvironment, cellular elements of the endoneurium were quantitatively and qualitatively assessed in rats receiving 0%, 10%, 20% or 40% galactose diets. After four months of galactose intoxication, dose-dependent changes in the size distribution of myelinated nerve fibers were apparent. A shift in size-frequency histograms of galactose-intoxicated animals towards smaller fibers was accompanied by a decrease in axon diameter and the volume fraction ratio of axon to myelinated nerve fibers. In the sciatic nerve of all 40% galactose-fed rats examined by electron microscopy, Schwann cells of myelinated fibers showed both reactive and degenerative changes. Demyelination was preceded by splitting at the intraperiod line. Remyelination was identified by axons with disproportionately thin myelin sheaths. Axonal dystrophy and degeneration were infrequently seen, but there was axonal regeneration. Dose-dependent increases in mast cell number were observed with degranulation apparent in rats receiving 20% and 40% galactose. Endothelial cell number and basal lamina thickness were increased in the endoneurial vessels of galactose-intoxicated rats. Increased cytoplasmic area and degenerative changes in pericytes were also noted. These observations indicate that significant morphologic changes accompany the hyperosmotic imbalance resulting from galactose intoxication of four months duration. Schwann cell injury and demyelination are present in a disorder linked to polyol metabolism since aldose reductase, the anabolic enzyme of the polyol pathway, is localized to this myelin-forming cell.
尽管长期以来人们一直怀疑糖尿病性神经病变中雪旺氏细胞会受到损伤，但慢性高血糖和多元醇途径激活对雪旺氏细胞的影响尚未明确。由持续四个月的半乳糖中毒引起的高血糖会导致神经内膜液中钠和氯的剂量依赖性积聚，这与多元醇途径活性有关，并伴有坐骨神经含水量、神经内膜液压和（钠 +，钾 +）-ATP 酶活性的剂量依赖性增加。为了了解这些变化对神经微环境的影响，对接受 0%、10%、20%或 40%半乳糖饮食的大鼠的神经内膜细胞成分进行了定量和定性评估。半乳糖中毒四个月后，有髓神经纤维大小分布出现剂量依赖性变化。半乳糖中毒动物的大小频率直方图向较小纤维方向偏移，同时轴突直径和轴突与有髓神经纤维的体积分数比降低。在所有经电子显微镜检查的 40%半乳糖喂养大鼠的坐骨神经中，有髓纤维的雪旺氏细胞出现了反应性和退行性变化。脱髓鞘之前在周期间线处出现分裂。通过髓鞘不成比例变薄的轴突可识别出再髓鞘化。轴索性营养不良和变性很少见，但有轴突再生。观察到肥大细胞数量呈剂量依赖性增加，在接受 20%和 40%半乳糖的大鼠中明显可见脱颗粒现象。半乳糖中毒大鼠的神经内膜血管中内皮细胞数量和基膜厚度增加。还注意到周细胞的细胞质面积增加和退行性变化。这些观察结果表明，持续四个月的半乳糖中毒导致的高渗失衡伴随着显著的形态学变化。雪旺氏细胞损伤和脱髓鞘存在于与多元醇代谢相关的疾病中，因为多元醇途径的合成酶醛糖还原酶定位于这种形成髓鞘的细胞。
