Department of Otolaryngology-Head and Neck Surgery and Communicative Disorders, School of Medicine, University of Louisville, Louisville, KY, United States of America.
Department of Otolaryngology-Head and Neck Surgery, University of Missouri School of Medicine, Columbia, MO, United States of America.
PLoS One. 2023 Jun 23;18(6):e0287044. doi: 10.1371/journal.pone.0287044. eCollection 2023.
Swallowing impairment is a major complication of radiation treatment for oropharyngeal cancers. Developing targeted therapies that improve swallowing outcomes relies on an understanding of the mechanisms that influence motor function after radiation treatment. The purpose of this study was to determine whether there is a correlation between radiation induced changes in tongue movement and structural changes in irradiated submental muscles, as well as assess other possible causes for dysfunction. We hypothesized that a clinically relevant total radiation dose to the submental muscles would result in: a) quantifiable changes in tongue strength and displacement during drinking two months post treatment; and b) a profibrotic response and/or fiber type transition in the irradiated tissue. Sprague-Dawley adult male rats received radiation to the submental muscles at total dose-volumes known to provoke dysphagia in humans. A clinical linear accelerator administered 8 fractions of 8Gy for a total of 64Gy. Comparisons were made to sham-treated rats that received anesthesia only. Swallowing function was assessed using videofluoroscopy and tongue strength was analyzed via force lickometer. TGFβ1 expression was analyzed via ELISA. The amount of total collagen was analyzed by picrosirius red staining. Immunofluorescence was used to assess fiber type composition and size. Significant changes in licking function during drinking were observed at two months post treatment, including a slower lick rate and reduced tongue protrusion during licking. In the mylohyoid muscle, significant increases in TGFβ1 protein expression were found post radiation. Significant increases in the percentage of collagen content were observed in the irradiated geniohyoid muscle. No changes in fiber type expression were observed. Results indicate a profibrotic transition within the irradiated swallowing muscles that contributes to tongue dysfunction post-radiation treatment.
吞咽障碍是头颈部癌症放射治疗的主要并发症。开发能改善吞咽结果的靶向治疗方法依赖于对影响放射治疗后运动功能的机制的理解。本研究的目的是确定舌运动的放射诱导变化与照射下颌下肌的结构变化之间是否存在相关性，以及评估其他可能导致功能障碍的原因。我们假设，下颌下肌肉的临床相关总放射剂量将导致：a）治疗后两个月在饮水期间舌强度和位移的可量化变化；和 b）照射组织中的纤维型转化和/或纤维型转化。Sprague-Dawley 成年雄性大鼠接受下颌下肌肉的放射治疗，剂量-体积与人类引起吞咽困难的剂量-体积相当。临床直线加速器给予 8 次 8Gy 的 8 个分数，总剂量为 64Gy。与仅接受麻醉的假处理大鼠进行比较。使用荧光透视法评估吞咽功能，通过力舔计分析舌强度。通过 ELISA 分析 TGFβ1 的表达。通过苦味酸红染色分析总胶原蛋白的量。免疫荧光用于评估纤维类型组成和大小。在治疗后两个月观察到饮水期间舔舐功能的显著变化，包括舔舐速度较慢和舌伸出减少。在下颌舌骨肌中，发现放射后 TGFβ1 蛋白表达显著增加。在照射的颏舌肌中观察到胶原蛋白含量的百分比显著增加。未观察到纤维类型表达的变化。结果表明，在放射后的吞咽肌肉中存在致纤维化转变，这导致了舌功能障碍。
