TREATMENT AND PREVENTION OF IMPOTENCE

这项研究计划的长期目标是开发最好的 治疗人类勃起功能障碍的策略， 与这种疾病相关的分子机制。 这个的主要目标 该项目旨在阐明阳痿相关的分子机制， 以大鼠为实验动物， 模型 该项目的理由是，阴茎神经损伤和 衰老可能在阳痿中起重要作用，因此了解 这个过程将有助于治疗这种疾病。 这项建议 是基于阴茎神经损伤和衰老相关的假设 阳痿可能是由于非肾上腺素能非胆碱能 血管舒张系统，一氧化氮合酶，鸟苷酸环化酶和环 GMP介导的机制。 这一假设将通过 追求以下具体目标：1）调查的作用 阴茎神经损伤和衰老对非肾上腺素能、非胆碱能 血管扩张系统与勃起功能障碍有关。 这 目的将通过检查阴茎神经的神经解剖学来实现 通过NADPH黄递酶（一氧化氮合酶）使用免疫组织化学， 光学和电子显微镜。 2)为了阐明 与神经损伤和衰老介导的阳痿有关。 这 通过测定一氧化氮合酶活性， （酶法），免疫组织化学），一氧化氮基因表达 （北方印迹，RNA酶保护试验），鸟苷酸环化酶，和环 GMP。 3)探讨神经生长因子在再生中的作用 非肾上腺素能非胆碱能神经的损伤。 这一目标 将通过切除海绵体神经和慢性 通过植入的渗透泵施用神经生长因子。 的 用一氧化氮合酶检测神经再生过程 染色和光学和电子显微镜检查。 完成这些 实验将清楚地阐明阳痿的分子机制 与阴茎神经损伤和衰老有关。 该提案还将 探讨神经生长因子在海绵体神经再生中的作用 这可能有助于治疗勃起功能障碍相关的 神经损伤

The long-term objective of this research proposal is to develop the best strategy for treating human erectile dysfunction by understanding the molecular mechanisms associated with this disease. The main goal of this project is to elucidate the molecular mechanisms of impotence associated with penile nerve injury and aging, using rats as an experimental animal model. The rational for this project is that penile nerve injury and aging may play an important role in impotence and therefore understanding of this process will help in treatment of this disease. This proposal is based on the hypothesis that penile nerve injury and aging associated impotence may be due to alteration in nonadrenergic noncholinergic vasodilator system, nitric oxide synthase, guanylate cyclase and cyclic GMP mediated mechanisms. This hypothesis will be achieved through pursuit of the following specific aims: 1) To investigate the role of penile neural injury and aging on nonadrengergic, noncholinergic vasodilator system which is associated with erectile dysfunction. This objective will be achieved by examining the neuroanatomy of penile nerves by NADPH diaphorase (nitric oxide synthase) using immunohistochemistry, light and electron microscopy. 2) To elucidate the molecular mechanisms associated with nerve injury and aging mediated impotence. This objective will be achieved by determining nitric oxide synthase activity (enzymatic assay), immunohistochemistry), nitric oxide gene expression (Northern blot, RNase protection assay), guanylate cyclase, and cyclic GMP. 3) To investigate the role of nerve growth factor in regeneration of nonadrenergic noncholinergic nerves after neurotomy. This objective will be achieved by denervating cavernous nerves and chronic administration of nerve growth factor by an implanted osmotic pump. The nerve regeneration process will be examined by nitric oxide synthase staining and light and electron microscopy. The accomplishment of these experiments will clearly elucidate the molecular mechanisms of impotence associated with penile nerve injury and aging. This proposal will also investigate the nerve growth factor in regeneration of cavernous nerves which might help in treatment of erectile dysfunction associated with nerve injury.