LEUPEPTIN IN RECOVERY AFTER NERVE REPAIR

这项研究解决了钙激活中性的影响。 亮胃素三肽对肌肉和肌肉的抑制作用 1)初级和2)延迟初级后的周围神经， 灵长类卷尾猴的神经外膜缝合(神经修复) 猴子模型(Cebus Apella)。我们的联合组织学， 超微结构、生化、毒理学和功能研究 旨在确认和扩展亮肽素在体内的作用 对肌肉和神经钙激活中性的抑制作用 蛋白酶。这种酶已经令人信服地牵连到 同时介导沃勒氏变性和继发性失神经 肌肉萎缩。周围神经损伤后对该酶的抑制作用 修复有促进神经肌肉功能恢复的潜力。 我们建议研究亮肽素对血管内皮细胞生长的抑制作用 原发性和延迟性初级神经外膜后的退行性事件 通过a)光和电子的标准技术进行神经修复 显微镜；b)通过免疫组织化学技术检测 钙激活中性蛋白水解酶；以及c)通过 纤维连接蛋白相关蛋白的免疫组织化学技术 肌纤维和雪旺细胞中的基膜。另外，d) 生化研究的目的是回答亮肽素是否 抑制肌肉中的蛋白水解酶将改善外观 一种特定形式的端板乙酰胆碱酯酶(16S)，它是 肌肉有效神经再支配的标志。此外，e)马达 感觉神经传导速度评估计划如下 初次和延迟性神经再支配的功能评价 一期神经修复和亮肽素治疗。最后，f)系列 亮肽素给药后的毒理学和吸收研究 都是有计划的。 我们研究的目标是进一步测试亮肽作为一种 外周原发和延迟原发的辅助治疗 神经修复有助于更早和更有效地恢复 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.