LEUPEPTIN IN RECOVERY AFTER NERVE REPAIR

本研究探讨了钙激活中性粒细胞的影响， 三肽亮抑酶肽对肌肉的蛋白酶抑制， 外周神经在1）原发性和2）延迟原发性之后， 灵长类卷尾猴的神经外膜缝合（神经修复） 猴模型（Cebus apella）。 我们结合组织学， 超微结构、生物化学、毒理学和功能研究 旨在确认和扩大亮抑酶肽的体内 抑制肌肉和神经钙激活中性 蛋白酶 这种酶已经令人信服地与 介导沃勒变性和继发性去神经支配 肌肉萎缩 外周神经损伤后， 修复具有增强神经肌肉恢复的潜力。 我们建议研究亮抑酶肽对 原发性和迟发性原发性神经外膜损伤后的退行性事件 通过a）光和电子中的标准技术进行神经修复 B）通过免疫组织化学技术检测 钙激活的中性蛋白酶;和c）通过 免疫组化技术检测纤维连接蛋白 肌纤维和雪旺细胞的基底层。 （d） 生物化学研究旨在回答亮抑酶肽是否 抑制肌肉中的蛋白酶将增强外观 一种特殊形式的终板乙酰胆碱酯酶（16 S）， 肌肉有效神经再支配的标志物。 E.电动机 和感觉神经传导速度评估计划为 初次和延迟后神经再支配的功能评估 初级神经修复和亮抑酶肽治疗。 F）系列 亮抑酶肽给药后的毒理学和吸收研究 都计划好了 我们研究的目的是进一步测试亮抑酶肽作为一种 外周原发性和延迟原发性的连续治疗 神经修复有助于更早更有效地恢复 功能

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.