Schuschereba S T, Bowman P D, Vargas J A, Johnson T W, Woo F J, McKinney L
Letterman Army Institute of Research, Presidio of San Francisco, California 94129-6800.
Toxicol Pathol. 1990;18(3):387-95. doi: 10.1177/019262339001800305.
To determine if alterations in extraocular muscle morphology occur after subchronic oral administration of pyridostigmine bromide, rats were continuously fed 90 mg/kg in meal and examined at 1, 2, 4, 7, and 15 days. Within the first day, blood acetylcholinesterase activity was reduced by 87% and remained inhibited by 74-91% during the study. Light microscopy demonstrated that by day 1 approximately 3% of the extraocular myofibers were shrunken and invaded by inflammatory cells. The most severe degenerative changes consisting of vacuoles and inflammatory cell infiltration occurred at day 1 with progressively less severe changes at days 2 and 4. At days 7 and 15, 1.3-4.5% of the myofibers still exhibited damage. Ultrastructurally, all presynaptic areas were normal but the postsynaptic areas of affected myofibers at days 1, 2, and 4 showed myofilament and Z-band dissolution, mitochondrial inclusions, subneural fold and T-tubule/sarcoplasmic reticulum vacuolization and subneural fold depth reduction. By days 7 and 15, these changes were diminished in some cases and in others alterations appeared similar to day 1. We conclude that subchronic feeding of pyridostigmine bromide induces myopathic rather than neurogenic changes in rat extraocular muscle and that the myopathy is different in these muscles than in the diaphragm from the the same rats.
为了确定在亚慢性口服溴吡斯的明后眼外肌形态是否会发生改变，给大鼠连续喂食90mg/kg的该药物，并在第1、2、4、7和15天进行检查。在第一天内，血液乙酰胆碱酯酶活性降低了87%，并且在研究期间一直受到74%-91%的抑制。光学显微镜显示，到第1天时，约3%的眼外肌纤维出现萎缩并被炎性细胞侵入。最严重的退行性变化包括空泡形成和炎性细胞浸润，发生在第1天，在第2天和第4天变化逐渐减轻。在第7天和第15天，1.3%-4.5%的肌纤维仍表现出损伤。超微结构上，所有突触前区域均正常，但在第1、2和4天，受影响肌纤维的突触后区域显示肌丝和Z带溶解、线粒体包涵体、神经下褶和T管/肌浆网空泡化以及神经下褶深度降低。到第7天和第15天，这些变化在某些情况下有所减轻，而在另一些情况下，变化似乎与第1天相似。我们得出结论，亚慢性喂食溴吡斯的明会在大鼠眼外肌中诱导肌病性而非神经源性变化，并且这些肌肉中的肌病与同一只大鼠的膈肌中的肌病不同。
