Bowman P D, Schuschereba S T, Johnson T W, Woo F J, McKinney L, Wheeler C R, Frost D, Korte D W
Letterman Army Institute of Research, Presidio of San Francisco, California 94129-6800.
Fundam Appl Toxicol. 1989 Jul;13(1):110-7. doi: 10.1016/0272-0590(89)90311-4.
To determine if alterations in muscle morphology occur after subchronic oral administration of pyridostigmine bromide, rats were fed 90 mg/kg continuously in meal and examined at 1, 2, 4, 7, and 15 days. Within the first day, cholinesterase activity was reduced by 87% and remained inhibited by 74-91% for the entire course of the feeding. Light microscopy demonstrated that by the first day approximately 1 in 100 myofibers was shrunken and contained centralized nuclei. Electron microscopic examination showed that while presynaptic areas of neuromuscular junctions were relatively unaffected by this dose, postsynaptic areas invariably showed maximal changes. Ultrastructural alterations included disruption of myofilaments, mitochondrial changes consistent with accumulation of calcium, and nuclear alterations. These effects appeared not to be cumulative and were greatly diminished by 15 days even under constant drug administration and inhibition of cholinesterase activity. We conclude that subchronic feeding of pyridostigmine bromide induces primarily myopathic rather than neurogenic changes in the diaphragm and that some mechanism of accommodation may be activated that minimizes continued muscle injury.
为了确定在亚慢性口服溴吡斯的明后肌肉形态是否会发生改变，给大鼠连续喂食90mg/kg的溴吡斯的明，并在第1、2、4、7和15天进行检查。在第一天内，胆碱酯酶活性降低了87%，并且在整个喂食过程中一直受到74%-91%的抑制。光学显微镜显示，到第一天时，大约每100根肌纤维中有1根萎缩并含有中央核。电子显微镜检查表明，虽然该剂量对神经肌肉接头的突触前区域影响相对较小，但突触后区域总是出现最大变化。超微结构改变包括肌丝破坏、与钙积累一致的线粒体变化以及核改变。这些影响似乎不是累积性的，即使在持续给药和抑制胆碱酯酶活性的情况下，到15天时这些影响也大大减轻。我们得出结论，亚慢性喂食溴吡斯的明主要在膈肌中诱导肌病性而非神经源性变化，并且可能激活了某种适应机制，从而使肌肉持续损伤最小化。
