MOLECULAR STUDIES OF EXPERIMENTAL DIABETIC NEUROPATHY

描述(改编自申请者摘要)：超过50% 糖尿病患者有勃起功能障碍，并有自主神经病变 扮演着近邻的角色。然而，自主神经的确切贡献 糖尿病勃起功能障碍的神经病变仍未明确。部分内容 难以确定自主神经系统的病因学作用 糖尿病患者的勃起功能障碍与阴茎 具有保存合体组织功能的多种机制。在……里面 特别是：1.神经元的神经支配；2.细胞与细胞之间的相互作用 3.肌源性细胞内信号转导过程。 对保证各种生理功能的勃起功能至关重要 条件。这种可塑性被认为是一个对人类生存至关重要的器官 男性和他们的性伴侣的物种和生理健康。 这些研究的明确目的是利用已建立的大鼠模型 实验性糖尿病神经病变评价糖尿病对神经病变的影响 阴茎的自主神经支配，以及任何与此相关的变化 细胞间通讯和生肌反应性。特别是，我们将 检验自主神经病变与全脑 组织功能的改变，这至少部分是由改变引起的 In离子流过钾(K)和缝隙连接通道。具体来说，我们 将在Fischer-344中诱导1-6个月的链脲佐菌素(STZ)糖尿病 (F-344)大鼠，以及：1.评估分子变化的功能相关性 与实验性糖尿病相关的K通道和缝隙连接 神经病变/高血糖，以及2.评估 一种新的K通道和缝隙连接的分子变化 改善勃起功能障碍的基因治疗方法。对这件事 最后，我们将利用各种技术，从体内动物研究到 组织、细胞、亚细胞和分子/遗传学的体外研究 级别。通过将如此多样化的技术应用于 我们希望对重要的医学问题有最大的了解 在体内，这种功能与分子变化的量化程度密切相关。

DESCRIPTION (Adapted from the Applicant's Abstract): More than 50 percent of patients with diabetes have erectile dysfunction, with autonomic neuropathy playing a proximal role. However, the precise contribution of autonomic neuropathy to diabetic erectile dysfunction remains undefined. Part of the difficulty in establishing the etiologic role of the autonomic nervous system in diabetic erectile dysfunction is related to the fact that the penis is endowed with multiple mechanisms for preserving syncytial tissue function. In particular, the interaction among: 1. neuronal innervation, 2. cell-to-cell communication, and 3. myogenic intracellular signal transduction processes, are critical to guarantee erectile function over a wide range of physiological conditions. Such plasticity is expected of an organ critical to the survival of the species and the physiological well being of men and their sexual partners. The explicit aim of these studies is to utilize an established rat model of experimental diabetic neuropathy to evaluate the effects of diabetes on autonomic innervation in the penis, and any correlative changes that occur in intercellular communication and myogenic responsivity. In particular, we will test the hypothesis that autonomic neuropathy is associated with global alterations in tissue function, that result, at least in part, from alterations in ion flow through potassium (K) and gap junction channels. Specifically, we shall induce a 1-6 month period of streptozotocin (STZ)-diabetes in Fischer-344 (F-344) rats, and: 1. Evaluate the functional correlates of molecular changes in K channels and gap junctions that are associated with experimental diabetic neuropathy/hyperglycemia, and 2. To evaluate the functional correlates of the molecular changes in K channels and gap junctions that are produced by a novel gene therapy approach for the amelioration of erectile dysfunction. To this end, we will utilize techniques ranging from in vivo animal studies, through in vitro studies at the tissue, cellular, subcellular and molecular/genetic levels. By bringing to bear such a diverse array of techniques on this important medical problem we hope to gain the greatest insight possible into the functional correlates in vivo of well quantified molecular alterations.