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

描述(申请人提供)：声带振动对损伤后声带重塑的影响还知之甚少。在临床上，这导致在术后发声使用、发声休息以及对接受显微手术的患者缺乏临床护理标准方面几乎没有达成一致意见。从历史上看，支持发声休息的理论认为发声与创伤有关，伤口愈合延迟。相比之下，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反应良好。在这项应用中，我们将1)在兔创伤后动物模型中诱导发声，2)测量35分钟和120分钟发声对受伤声带上皮覆盖之前I型胶原原、胶原、纤维连接蛋白和糖胺聚糖透明质酸等蛋白产物的基因表达和组织水平的影响。我们将证明，脑和神经刺激技术为诱导兔发声提供了合适的方法。我们假设，损伤后72小时开始发声的120分钟导致纤维连接蛋白和胶原水平显著升高，而损伤后72小时开始发声的35分钟导致I型胶原原、胶原、纤维连接蛋白和透明质酸水平与对照组相比稳定。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给药策略提供理论基础，这些研究将调查受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。这项研究计划可能会对临床产生影响，因为它提供了数据来支持有关术后发声的临床护理标准。 项目简介：疤痕是声带手术的不良并发症。声音的使用对疤痕声带伤口愈合的影响在很大程度上是未知的。这项研究的目的是了解发声如何影响伤口愈合，以便为术后发声的护理提供循证标准。

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.