Norido F, Canella R, Zanoni R, Gorio A
Exp Neurol. 1984 Feb;83(2):221-32. doi: 10.1016/S0014-4886(84)90094-3.
We studied the development of diabetic neuropathy and its treatment with gangliosides using the C57BL/Ks mouse. The results of axonal morphometry showed the presence of a progressive axonal atrophy which was maximal at 180 days of age. To 400 days of age there was no longer any significant difference, perhaps due to aging processes. Nerve conduction velocity changed significantly from the early days of life. Thirty-day treatment with gangliosides significantly improved nerve conduction velocity and axonal morphometry at 180 and 280 days of life. No effect was observed with treatments at 30 or 60 days. It was previously shown that the early phase of the C57BL/Ks mouse neuropathy was reversed by insulin, whereas the late phase (180 days) was not. We showed elsewhere that at 180 days of age in the C57BL/Ks mouse there was a drastic decrease in slow transport of AChE (G1 and G2 molecular forms) indicating a shift in neuronal metabolism and suggesting that the disease was then more intrinsically neuronal. Using the suggestion of Robertson and Sima (Diabetes 29: 60-67, 1980) we label the first phase of the neuropathy "metabolic" (treatable with insulin) and the second phase "neuronal" (treatable with gangliosides). This "neuronal" phase could be related to the degenerative stage of human diabetic neuropathy.
我们使用C57BL/Ks小鼠研究了糖尿病性神经病变的发展及其用神经节苷脂的治疗情况。轴突形态测量结果显示存在进行性轴突萎缩，在180日龄时最为明显。到400日龄时不再有任何显著差异，这可能是由于衰老过程所致。神经传导速度从生命早期就有显著变化。用神经节苷脂进行30天治疗可显著改善180日龄和280日龄时的神经传导速度和轴突形态测量结果。在30天或60天进行治疗未观察到效果。先前已表明，胰岛素可逆转C57BL/Ks小鼠神经病变的早期阶段，而晚期阶段（180天）则不能。我们在其他地方表明，在C57BL/Ks小鼠180日龄时，乙酰胆碱酯酶（G1和G2分子形式）的慢速运输急剧下降，这表明神经元代谢发生了变化，并提示该疾病在那时更具神经元内在性。根据罗伯逊和西马的建议（《糖尿病》29: 60 - 67, 1980），我们将神经病变的第一阶段标记为“代谢性”（可用胰岛素治疗），第二阶段标记为“神经元性”（可用神经节苷脂治疗）。这个“神经元性”阶段可能与人类糖尿病性神经病变的退行性阶段有关。
