EFFECTS OF LEUPEPTIN ON RECOVERY AFTER NERVE REPAIR

亮肽素对神经修复后恢复的影响

• 批准号: 3404629
• 负责人: LAWRENCE HURST
• 金额: $ 13.39万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-01 至 1988-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3404629
• 关键词: acetyl coA acetyltransferase; atrophy; biopsy; calcification stimulant; denervation; disease /disorder model; dissection; dosage; drug adverse effect; drug metabolism; histochemistry /cytochemistry; innervation; limbs; model design /development; muscle disorders; muscle metabolism; neuropharmacology; oligopeptides; peripheral nervous system disorders; protease inhibitor; wallerian degeneration

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.

本研究讨论了巯基蛋白酶抑制剂的作用， Leupeptin在神经外膜治疗前后对肌肉和周围神经的影响 灵长类动物模型中的神经缝合术（神经修复）。 我们的组织学和 超微结构的研究集中在亮抑酶肽的潜在抑制作用， 对神经和肌肉钙激活中性蛋白酶（CANP）的影响。 这种酶与部分介导沃勒氏 变性和继发性失神经肌肉萎缩。 我们建议 研究亮抑酶肽抑制这些变性 通过使用光学和电子显微镜中的标准技术， 免疫组织化学超微结构方法。 使用后者 技术，钙激活中性蛋白酶的组织位点，正常人， 肌肉和神经将被确定。 接下来，这个分布 将研究神经修复和亮抑酶肽治疗后的蛋白酶。 此外，乙酰胆碱受体分布将在 受神经支配和去神经支配的肌肉对亮抑酶肽治疗的反应。 肌内注射亮抑酶肽后的系列毒理学和吸收研究 行政规划。 获得的信息可能会给我们一个更好的 深入了解神经修复后的神经肌肉变性。 的 这项研究的长期目标是检查亮抑酶肽作为一种 术后促进神经肌肉恢复的连续疗法 显微外科修复周围神经损伤。