Effect of Vocalization on Tissue Protein Levels in the Acute Vocal Fold Wound

描述（由申请人提供）：声带振动对损伤后声带重塑的影响知之甚少。在临床上，这导致了非常小的协议，术后语音使用，语音休息，并缺乏一个标准的临床护理接受phonomicrosurgery患者。从历史上看，声音休息的支持一直是由理论驱动的，涉及发声相关的创伤延迟伤口愈合。相反，最近的体外研究表明，细胞外基质基因的基因表达水平对机械负荷的反应有利。在本申请中，我们将1）在受伤后的兔动物模型中诱发发声，和2）在上皮覆盖受伤的声带之前，测量35分钟和120分钟剂量的发声对蛋白质产物前胶原I、胶原、纤连蛋白和糖胺聚糖透明质酸的基因表达和组织水平的影响。我们将证明，大脑和神经刺激技术提供了合适的方法，引发在兔子发声。我们假设，120分钟的发声损伤后72小时开始在纤连蛋白和胶原蛋白的水平显着升高，而35分钟的发声损伤后72小时开始在稳定的前胶原蛋白I，胶原蛋白，纤连蛋白，透明质酸相对于对照组的水平。这些实验将导致兔体内发声模型的开发和用于下一系列研究的给药策略的基本原理，所述下一系列研究将研究在损伤声带的上皮完全覆盖后开始的发声对基因表达和细胞外基质沉积的影响。这项研究的长期目标是了解发声如何影响受伤声带的组织和重塑。这项研究计划可能会产生临床影响，提供数据，以支持有关术后语音使用的临床护理标准。 项目叙述：瘢痕是声带手术的不良并发症。声音使用对声带创伤愈合的影响在很大程度上是未知的。本研究的目的是了解声音使用如何影响伤口愈合，以便提供有关术后声音使用的循证护理标准。

DESCRIPTION (provided by applicant): The effect of vocal fold vibration on remodeling of the vocal fold after injury is poorly understood. Clinically, this has resulted in very little agreement with regard to post-operative voice use, voice rest, and lack of a standard of clinical care for patients undergoing phonomicrosurgery. Historically, support for voice rest has been driven by theories that implicate phonation associated trauma with delayed wound healing. In contrast, recent in-vitro studies have shown that gene expression levels of extracellular matrix genes respond favorably to mechanical load. In this application we will 1) Elicit vocalization in a rabbit animal model post-wounding and 2) measure the effects of a 35 minute and 120 minute dose of vocalization on gene expression and tissue levels of the protein products pro-collagen I, collagen, fibronectin, and the glycosaminoglycan hyaluronan prior to epithelial coverage of the wounded vocal fold. We will demonstrate that brain and nerve stimulation techniques provide suitable methods for eliciting vocalization in the rabbit. We hypothesize that 120 minutes of vocalization initiated 72 hours after injury results in significantly elevated levels of fibronectin and collagen, while 35 minutes of vocalization initiated 72 hours after injury results in stable levels of pro-collagen I, collagen, fibronectin, and hyaluronan relative to control. These experiments will result in the development of a rabbit in- vivo phonation model and rationale for a dosing strategy to be used in the next series of studies that will investigate the effects of vocalization initiated after complete epithelial coverage of the wounded vocal fold on gene expression and extracellular matrix deposition. The long-term objective of this line of research is to understand how vocalization influences organization and remodeling of the injured vocal fold. This research program may have an impact clinically by providing data to support a standard of clinical care regarding post- operative voice use. Project Narrative: Scarring is an adverse complication of vocal fold surgery. The effect of voice use on wound healing of the scarred vocal fold is largely unknown. The goal of this research is to understand how voice use influences wound healing in order to provide an evidence-based standard of care regarding post-operative voice use.