Biochemical studies on the pathogenetic mechanism of toxic neuropathies by using axonal transport.

各种神经毒性化学物质被认为根据其主要目标被分为几类。其中选择了三个主要基团，建立了体内模型系统，研究了它们的生化作用机制。通过分析这些药物影响下的缓慢轴突运输，得到了以下结果。秋水仙碱的神经毒性：秋水仙碱完全和唯一地阻断微管蛋白的运输，而不影响肌动蛋白和神经丝蛋白的运输。7周龄大鼠第五腰背根神经节注射秋水仙碱4g后，几乎所有无髓轴突和一小部分有髓轴突变性，治疗后4天内开始再生。同时微管蛋白转运也恢复正常。亚氨基二丙腈的神经毒性：在腹腔注射剂量为1.5g/kg体重的IDPN几天后出现神经症状。在这种情况下，神经丝蛋白的轴突运输受到严重抑制，而微管蛋白和肌动蛋白的轴突运输没有任何干扰。IDPN治疗6周后神经丝转运恢复正常，但神经功能异常始终未见恢复。丙烯酰胺的神经毒性：大鼠饮用200ppm的丙烯酰胺13周后，慢轴突运输的所有成分均明显加速。这一发现被解释为轴突变性和再生的结果。2，5-己二酮：2，5-己二酮的神经毒性导致神经细丝转运速率增加，即使在给药早期无症状的情况下，微管蛋白和肌动蛋白的转运速率也没有变化。二硫化碳的神经毒性：这种药物对神经丝运输的影响与2，5-己二酮相似。

Various neurotoxic chemicals are thought to be classified into several groups according to their main targets. Among them three major groups were chosen and in vivo model systems were developed to investigate their biochemical mechanism of action. By analysing slow axonal transport under the influence of these drugs, the following results were obtained.u. Neurotoxicity of colchicine:Colchicine completely and exclusively blocks tubulin transport, without affecting that of actin and neurofilament proteins. when 4 g of colchicine is injected into fifth lumbar dorsal root ganglion of 7 week-old rat, almost all unmyelinated axons as well as a small portion of myel-nated ones are degenerated, then start regenerating within 4 days after treatment. At the same time tubulin transport also recovers to normal.2. Neurotoxicity of , '-iminodipropionitrile:Neurological symptoms develop a few days after an intraperitoneal injection of IDPN with dose of 1.5g/kg of body weight. Under these conditions axonal transport of neurofilament proteins is severely inhibited, without any disturbance of that of tubulin and actin. Neurofilament transportbecomes normal 6 weeks after IDPN administration, thoughneurological abnormalities never show recovery.3. Neurotoxicity of acrylamide:Marked acceleration of all components of slow axonal transport is found in rats after 13 week-administration of acrylamide with dose of 200 ppm in drinking water. This finding is interpreted to be the results of axonal degeneration and regeneration.4. Neurotoxicity of 2,5-hexanedione:2, 5-Hexanedione causes an increase of rate of neurofilament transport, leaving that of tubulin and actin unchanged even in early stage of administration when no symptom appears.5. Neurotoxicity of carbon disulfide:This drug shows a similar effect on neurofilament transport to that of 2, 5-hexanedione.