Chen Guangjin, Lechien Jérôme R
Department of Surgery, UMONS Research Institute for Health Sciences and Technology, University of Mons (UMons), Mons, Belgium.
Department of Surgery, UMONS Research Institute for Health Sciences and Technology, University of Mons (UMons), Mons, Belgium; Department of Otolaryngology and Head and Neck Surgery, Foch Hospital, School of Medicine, UFR Simone Veil, Université Versailles Saint-Quentin-en-Yvelines (Paris Saclay University), Paris, France; Department of Otolaryngology and Head and Neck Surgery, CHU Saint-Pierre, Brussels, Belgium; Department of Otolaryngology, Elsan Hospital of Poitiers, Poitiers, France.
J Voice. 2025 Apr 15. doi: 10.1016/j.jvoice.2025.03.046.
Over the past decades, various animal models have been developed to elucidate the molecular pathways and tissue alterations associated with laryngopharyngeal reflux disease (LPRD). This systematic review aimed to summarize the current knowledge gained through experimental animal models in understanding LPRD pathophysiology, especially LPRD-related voice disorders.
According to the PRISMA statements, two investigators systematically search PubMed, Embase, and Web of Science databases for experimental studies investigating mucosa injuries or modifications related to LPRD refluxate, and their potential mechanistic associations with voice quality impairments.
Of 326 retrieved articles, 44 studies documented reflux-induced laryngeal mucosal changes, including 19 animal model studies (canine, porcine, rat, mice, and rabbit models). The exposure of laryngeal tissue to refluxate (pepsin, bile acids, and trypsin) was associated with microscopic tissue alterations, including epithelium disruption and inflammatory infiltrate, metaplasia, erosion, and ulceration. The mucosa alterations vary according to the anatomical sublocation (vocal folds, posterior commissure, and supraglottic and subglottic regions). Several cytokines have been identified as mucosal injury mediators. The microscopic modifications of laryngeal mucosa may cause damage to tissue and changes in cell function. The experimental models were limited to supine-positioned animals exposed to liquid refluxate. No studies addressed the potential effects of elastase, bile salts, trypsin, and lipases in nonacidic (weakly acidic or alkaline) gaseous environment.
Experimental animal models of LPRD supported vocal fold and laryngeal mucosal changes in response to acidic reflux exposure. However, the translational value of these findings is limited by distinct differences in reflux pathophysiology between human subjects and animal models.
在过去几十年中，已开发出各种动物模型以阐明与喉咽反流病（LPRD）相关的分子途径和组织改变。本系统评价旨在总结通过实验动物模型在理解LPRD病理生理学，特别是LPRD相关声音障碍方面获得的现有知识。
根据PRISMA声明，两名研究人员系统检索了PubMed、Embase和Web of Science数据库，以查找研究与LPRD反流物相关的黏膜损伤或改变及其与声音质量受损的潜在机制关联的实验研究。
在检索到的326篇文章中，44项研究记录了反流引起的喉黏膜变化，包括19项动物模型研究（犬、猪、大鼠、小鼠和兔模型）。喉组织暴露于反流物（胃蛋白酶、胆汁酸和胰蛋白酶）与微观组织改变有关，包括上皮破坏和炎性浸润、化生、糜烂和溃疡。黏膜改变因解剖亚部位（声带、后联合以及声门上和声门下区域）而异。几种细胞因子已被确定为黏膜损伤介质。喉黏膜的微观改变可能导致组织损伤和细胞功能变化。实验模型仅限于仰卧位暴露于液体反流物的动物。没有研究探讨弹性蛋白酶、胆盐、胰蛋白酶和脂肪酶在非酸性（弱酸性或碱性）气体环境中的潜在影响。
LPRD的实验动物模型支持了酸性反流暴露后声带和喉黏膜的变化。然而，这些发现的转化价值受到人类受试者和动物模型之间反流病理生理学明显差异的限制。
