EFFECTS OF LEUPEPTIN ON RECOVERY AFTER NERVE REPAIR

本研究探讨了硫醇蛋白水解酶抑制剂的作用。 外膜神经支配前后肌肉和周围神经中亮氨酸的变化 灵长类动物模型的神经缝合(神经修复)。我们的组织学和 亮肽素体内潜在抑制作用的超微结构研究 对神经和肌肉钙激活中性蛋白酶(CANP)的影响。 这种酶被认为部分地调节了沃勒氏病毒 变性和继发性失神经肌肉萎缩。我们建议 研究亮肽素对这些退行性疾病的抑制作用 通过使用光学和电子显微镜中的标准技术，如 以及免疫组织化学超微结构方法。使用后者 钙激活中性蛋白水解酶在正常人中的组织定位 肌肉和神经将被确定。下一步，这个分布 将对神经修复和亮肽素治疗后的蛋白酶进行研究。 此外，还将检查乙酰胆碱受体的分布 神经支配和失神经肌肉对亮肽素治疗的反应。 亮肽素肌肉注射后的系列毒理学和吸收研究 行政管理是有计划的。所获得的信息可能会给我们带来更好的 对神经修复后的神经肌肉变性的洞察。这个 这项调查的长期目标是将亮肽素作为一种 辅助治疗促进术后神经肌肉功能恢复 周围神经断端的显微外科修复。

This study addresses the effects of the thiol protease inhibitor, leupeptin, on muscle and peripheral nerve before and after epineural neurorrhaphy (nerve repair) in a primate model. Our histological and ultrastructural studies focus on leupeptin's potential inhibitory in vivo effects on neural and muscle calcium activated neutral protease (CANP). This enzyme has been implicated in partially mediating both Wallerian degeneration and secondary denervation muscle atrophy. We propose to investigate leupeptin's potential for inhibition of these degenerative events by use of standard techniques in light and electron microscopy, as well as, immunohistochemical ultrastructural methods. Using this latter technique, the tissue loci of calcium activated neutral protease in normal muscle and nerve will be determined. Next, the distribution of this protease after nerve repair and leupeptin treatment will be investigated. Additionally, acetylcholine receptor distribution will be examined in innervated and denervated muscle in response to leupeptin treatment. Serial toxicological and absorption studies after intramuscular leupeptin administration are planned. The information gained may give us a better insight into neuromuscular degeneration following nerve repair. The long-term goal of the investigation is to examine leupeptin as an adjunctive therapy for facilitating neuromuscular recovery after the microsurgical repair of severed peripheral nerves.