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尚不清楚。在临床上，这导致了关于术后声音使用、声音休息以及对接受显微声音手术的患者缺乏标准的临床护理的意见很少一致。从历史上看，支持声音休息的理论是由暗示发声与创伤有关的理论驱动的，创伤愈合延迟。相反，最近的体外研究表明，细胞外基质基因的表达水平对机械负荷有良好的反应。在这个应用中，我们将1)在受伤后的兔子动物模型中诱导发声，2)测量35分钟和120分钟的发声剂量对基因表达和蛋白产物前胶原蛋白、胶原蛋白、纤维连接蛋白和糖胺聚糖透明质酸的组织水平的影响，然后在受伤的声带上皮覆盖之前。我们将证明大脑和神经刺激技术为兔的发声提供了合适的方法。我们假设，在受伤72小时后开始发声120分钟会导致纤维连接蛋白和胶原蛋白水平显著升高，而在受伤72小时后开始发声35分钟会导致前胶原I、胶原蛋白、纤维连接蛋白和透明质酸水平相对于对照组保持稳定。这些实验将导致兔体内发声模型的发展，并为下一系列研究中使用的剂量策略提供依据，这些研究将研究损伤声带完全上皮覆盖后开始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损声带的组织和重塑。本研究计划可能通过提供数据来支持术后语音使用的临床护理标准，从而对临床产生影响。

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.