Cherian P V, Kamijo M, Angelides K J, Sima A A
Department of Internal Medicine, Michigan Diabetes Research and Training Center, University of Michigan Medical Center, Ann Arbor 48109, USA.
J Diabetes Complications. 1996 Jul-Aug;10(4):192-200. doi: 10.1016/1056-8727(95)00084-4.
Chronic nerve conduction showing in experimental diabetic neuropathy has been associated with decreased nodal Na+ permeability and an ultrastructurally identifiable loss of axo-glial junctions, which comprise the paranodal voltage channel barrier separating nodal Na+ channels from paranodal K+ channels. In human and experimental diabetic neuropathy these structural changes of the paranodal apparatus correlate closely with the nerve conduction defect. The present immunocytochemical study of the alpha-subunit of the Na+ channel examined whether the breach of the voltage channel barrier may account for a shift in the distribution of Na+ channels explaining decreased nodal Na+ permeability. Biobreeding Wistar (BB/W) rats diabetic for 4-8 months showed a progressive redistribution of nodal Na+ channels across the paranodal barrier into the paranodal and internodal domains which was associated with chronic nerve conduction slowing. The present data suggest that structural damage to the paranodal barrier system in diabetic nerve facilitates the lateral displacement of Na+ channels from the nodal axolemma thereby diminishing their nodal density and the nodal Na+ permeability associated with the chronic nerve conduction defect in experimental diabetes. These abnormalities were prevented by the treatment with an aldose reductase inhibitor, belonging to a class of drugs that, in neuropathic patients, improves nerve-conduction velocity and repairs axo-glial dysjunction of the paranodal apparatus.
实验性糖尿病神经病变中出现的慢性神经传导与节点钠通透性降低以及轴突-胶质连接的超微结构可识别性丧失有关，轴突-胶质连接构成了将节点钠通道与节旁钾通道分隔开的节旁电压通道屏障。在人类和实验性糖尿病神经病变中，节旁装置的这些结构变化与神经传导缺陷密切相关。目前对钠通道α亚基的免疫细胞化学研究探讨了电压通道屏障的破坏是否可能导致钠通道分布的改变，从而解释节点钠通透性降低的原因。患有糖尿病4至8个月的生物繁殖Wistar（BB/W）大鼠显示，节点钠通道逐渐跨过节旁屏障重新分布到节旁和结间区域，这与慢性神经传导减慢有关。目前的数据表明，糖尿病神经中节旁屏障系统的结构损伤促进了钠通道从节点轴膜的侧向移位，从而降低了它们的节点密度以及与实验性糖尿病慢性神经传导缺陷相关的节点钠通透性。用醛糖还原酶抑制剂治疗可预防这些异常，醛糖还原酶抑制剂属于一类药物，在神经病变患者中，这类药物可提高神经传导速度并修复节旁装置的轴突-胶质功能障碍。
