Investigating the role of systemic dehydration in vocal fold wound healing

研究全身脱水在声带伤口愈合中的作用

• 批准号: 10188367
• 负责人: ANUMITHA VENKATRAMAN
• 金额: $ 4.6万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-22 至 2022-06-21
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10188367
• 关键词: Acute; Adult; Alcian Blue; Behavior; Biological Process; Biomechanics; Body Weight; Chronic; Collagen; Dehydration; Dermal; Elastin; Epithelial; Extracellular Matrix; Fibroblasts; Fibrosis; Gene Expression; Gene Proteins; Genes; Health; Hematocrit procedure; Human; Hyaluronan; Hydration status; Inflammation; Inflammation Mediators; Inflammatory; Injury; Interleukin-6; Irritants; Kidney; Laboratories; Lasers; Light; Liquid substance; Literature; Maintenance; Mammals; Measures; Mediating; Modeling; Morphology; Natural regeneration; Operative Surgical Procedures; Outcome; Outcome Measure; Physiological Processes; Physiology; Plasma; Polymerase Chain Reaction; Predisposition; Process; Production; Property; Protocols documentation; Publishing; Rattus; Recovery; Renin; Reporting; Risk; Role; Skin Tissue; Skin injury; Stains; Stratified Squamous Epithelium; Tissues; Transforming Growth Factor beta; Up-Regulation; Voice; Water; Western Blotting; experience; experimental study; healing; male; overexpression; protein expression; restoration; skin wound; viscoelasticity; vocal cord; wound; wound healing

Project Abstract The role of hydration in maintaining vocal fold health is still not fully understood. But it is generally believed that increasing hydration can optimize vocal function while decreasing hydration can negatively impact vocal physiology. Dermal literature suggests that systemic dehydration may prolong inflammation and delay re- epithelization of injured skin tissue. This proposal broadly questions whether similar suboptimal outcomes are also observed in vocal fold tissue after systemic dehydration as compared to euhydration (normal hydration state). If these negative outcomes are observed, there may be adverse implications for restoration of vocal function following damage from injury, surgery, or phonotraumatic behaviors. Therefore, we will investigate the vocal fold wound healing processes of acute inflammation, extracellular matrix proliferation, and re- epithelization in dehydrated and euhydrated male rats following vocal injury. Systemic dehydration will be achieved through an ecologically-valid water restriction protocol for 11 days (N = 15). Conversely, euhydrated rats (n=15) will be provided water ad-libitum for 11 days. Vocal injury will be induced in all rats. Vocal fold wound healing outcomes will be measured on the 7th day following vocal injury. Specific Aim 1 will measure the gene and protein expression of inflammatory mediators in dehydrated and euhydrated rats following vocal fold injury. We hypothesize an upregulation of inflammatory mediators (TGF-β1 and IL-6) in dehydrated rats when compared to euhydrated rats. Quantitative-Polymerase Chain Reaction and Western Blotting will be used to measure gene and protein expression levels respectively. Specific aim 2 will characterize the vocal fold epithelia and extracellular matrix in dehydrated and euhydrated rats following vocal fold injury. We hypothesize incomplete stratified squamous epithelial layer, decreased distribution and quantity of collagen and hyaluronan, and inadequate fibroblast proliferation in dehydrated rats as compared to euhydrated controls. Histochemical stains (HE, Alcian Blue and Trichome stains) and staining analysis will be used to observe the morphology and hyaluronan content. Overall, findings demonstrating overexpression of inflammatory mediators, incomplete re-epithelization, and altered concentration of extracellular matrix constituents would suggest increased risk for susceptibility from external irritants, and altered vocal fold biomechanics. The proposed study will provide much needed evidence for the role of hydration in influencing vocal outcomes and shed a light on the effects of systemic dehydration on vocal fold healing following injury.

项目摘要 水合作用在保持声带健康的作用仍然没有完全理解。但人们普遍认为 增加水合作用可以优化发声功能，而减少水合作用会对发声产生负面影响。 physiology.皮肤病学文献表明，全身性脱水可能会延长炎症和延迟再发。 损伤皮肤组织的上皮化。这一提议广泛质疑类似的次优结果是否 与正常水合（正常水合）相比，在全身脱水后的声带组织中也观察到 州）。如果观察到这些负面结果，可能会对声带恢复产生不利影响。 功能损伤后，从损伤，手术，或phonotraulic行为。因此，我们将调查 声带伤口愈合过程中的急性炎症，细胞外基质的增殖，再 在脱水和水合正常的雄性大鼠声带损伤后的上皮形成。全身性脱水 通过生态有效的限水方案实现11天（N = 15）。相反， 大鼠（n=15）可自由饮水11天。在所有大鼠中诱导声带损伤。声带 在声带损伤后第7天测量伤口愈合结果。具体目标1将衡量 炎症介质在脱水和正常水化大鼠中的基因和蛋白表达 声带受伤后我们假设，炎症介质（TGF-β1和IL-6）的上调， 脱水大鼠与正常水分大鼠相比。定量聚合酶链反应和Western 将使用印迹法分别测量基因和蛋白质表达水平。具体目标2将 表征脱水和正常水化大鼠声带上皮和细胞外基质 声带受伤后我们假设不完全复层鳞状上皮层， 脱水大鼠胶原和透明质酸的分布和数量以及成纤维细胞增殖不足 与正常水化对照相比。组织化学染色（HE、阿尔新蓝和毛状体染色）和染色 将使用分析来观察形态学和透明质酸含量。总体而言，调查结果表明， 炎症介质的过度表达，不完全的上皮再生，以及 细胞外基质成分提示对外部刺激物敏感的风险增加， 声带生物力学改变拟议的研究将提供急需的证据， 水合作用对发声结果的影响，并阐明了系统性脱水对声带的影响 受伤后的愈合。

项目成果

The role of systemic dehydration in vocal fold healing: Preliminary findings.

• DOI: 10.1002/lio2.942
• 发表时间: 2022-12
• 期刊: LARYNGOSCOPE INVESTIGATIVE OTOLARYNGOLOGY
• 影响因子: 1.9
• 作者: Venkatraman, Anumitha;Hawkins, Jan;McCain, Robyn;Duan, Chenwei;do Nascimento, Naila Cannes;Cox, Abigail;Sivasankar, M. Preeti
• 通讯作者: Sivasankar, M. Preeti