LEUPEPTIN IN RECOVERY AFTER NERVE REPAIR

神经修复后亮肽素的恢复

• 批准号: 3404630
• 负责人: LAWRENCE HURST
• 金额: $ 14.55万
• 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 1991-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3404630
• 关键词: Ceboidea; acetyl coA acetyltransferase; atrophy; biopsy; calcification stimulant; denervation; disease /disorder model; dissection; dosage; drug adverse effect; drug metabolism; histochemistry /cytochemistry; histology; innervation; limbs; model design /development; muscle disorders; muscle metabolism; nervous system regeneration; neuropharmacology; nicotinic receptors; oligopeptides; peripheral nervous system disorders; protease inhibitor; thiols; wallerian degeneration

This study addresses the effects of calcium activated neutral protease inhibition by the tripeptide, leupeptin, on muscle and peripheral nerve after 1) primary and 2) delayed primary, epineural neurorrhaphy (nerve repair) in a primate Capuchin monkey model (Cebus apella). Our combined histological, ultrastructural, biochemical, toxicological and functional studies are designed to confirm and expand on leupeptin's in vivo inhibitory effects on muscle and neural calcium activated neutral protease. This enzyme has been convincingly implicated in mediating both Wallerian degeneration and secondary denervation muscle atrophy. Inhibition of this enzyme after peripheral nerve repair has potential for enhancement of neuromuscular recovery. We propose to investigate leupeptin's inhibition of the degenerative events after primary and delayed primary epineural nerve repair by a) standard techniques in light and electron microscopy; b) by immunohistochemical techniques for loci of calcium activated neutral protease; and c) by immunohistochemical techniques for fibronectin associated to basal laminae in myofibers and Schwann cells. Also, d) biochemical studies are designed to answer whether leupeptin's inhibition of the protease in muscle will enhance the appearance of a specific form of end-plate acetylcholinesterase (16S) which is a marker for efficient reinnervation of muscle. Further, e) Motor and sensory nerve conduction velocity evaluations are planned as functional assessment of reinnervation after primary and delayed primary nerve repair and leupeptin treatment. Finally, f) serial toxicological and absorption studies after leupeptin administration are planned. The goal of our studies is to further test leupeptin as an adjunctive therapy to peripheral primary and delayed primary nerve repair in facilitating an earlier and more efficient return to function.

这项研究探讨了钙激活中性的影响 三肽亮肽素对肌肉和肌肉的蛋白酶抑制作用 1) 原发性和 2) 延迟原发性后的周围神经， 灵长类卷尾猴的神经外神经缝合术（神经修复） 猴子模型（Cebus apella）。 我们的综合组织学， 超微结构、生物化学、毒理学和功能研究 旨在确认和扩展亮肽素的体内 对肌肉和神经钙激活中性的抑制作用 蛋白酶。 这种酶已被令人信服地涉及 介导华勒变性和继发性去神经支配 肌肉萎缩。 周围神经后抑制该酶 修复具有增强神经肌肉恢复的潜力。 我们建议研究亮肽素对 原发性和迟发性原发性神经外膜后退行性事件 通过 a) 光和电子标准技术修复神经 显微镜检查； b) 通过免疫组织化学技术检测基因座 钙激活中性蛋白酶； c) 通过 纤连蛋白相关的免疫组织化学技术 肌纤维和雪旺细胞中的基底层。 另外，d) 生化研究旨在回答亮肽素是否 抑制肌肉中的蛋白酶会改善外观 一种特定形式的终板乙酰胆碱酯酶 (16S) 肌肉有效神经支配的标记。 此外，e) 电机 感觉神经传导速度评估计划为 原发性和延迟性神经支配术后的功能评估 初级神经修复和亮肽素治疗。 最后，f) 串行 亮肽素给药后的毒理学和吸收研究 已计划。 我们研究的目标是进一步测试亮肽素作为 外周原发性和延迟原发性的辅助治疗 神经修复有助于更早、更有效地恢复 功能。