类固醇对临床前模型声带损伤后上皮细胞的急性影响

Gary Gartling, Lea Sayce, Zachary Zimmerman, Alysha Slater, Lizzie Hary, Wenqing Yang, Michele Santacatterina, Bernard Rousseau, Ryan C. Branski
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引用次数: 0

摘要

导言糖皮质激素(GCs)具有强效抗炎作用,是喉部疾病的常用处方药。然而,糖皮质激素对声带损伤后上皮形态和屏障功能的影响却被忽视,这可能是影响疗效的关键。本研究量化了 GCs 对损伤声带上皮形态和屏障功能的影响。我们试图进一步了解 GC 机制的生化过程,以完善治疗策略。损伤七天后,动物接受生理盐水、地塞米松、甲基强的松龙或曲安奈德的双侧 20 μL 脐内注射(每种情况 n = 15)。治疗后 1 天、7 天或 60 天,每种情况下均有 5 只兔子被安乐死。另外五只动物作为未受伤/未治疗的对照组。为了量化经上皮电阻(TEER),将 1 毫米的上皮活检组织放入乌星室。结果60天后,GC治疗维持的TEER水平与未受伤/未治疗的对照组相似。然而,与生理盐水处理的情况相比,三苯氧胺降低了 TEER。在所有损伤的室颤中,上皮增生通常在急性期持续存在。60 天时,只有地塞米松和曲安奈德能增加损伤 VF 的上皮深度;与未损伤/未处理的对照组相比,所有 GCs 都能增加上皮深度。此外,与生理盐水治疗相比,谷胱甘肽不会改变上皮深度,这表明谷胱甘肽与自然愈合反应一致。60 天后,GCs 表现出不同程度的 TEER 恢复和上皮增生,这可能是由于不同的药效学特征所致。
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Acute Effects of Steroids on Vocal Fold Epithelium Post‐injury in a Preclinical Model
IntroductionGlucocorticoids (GCs) are commonly prescribed for laryngeal indications due to their potent anti‐inflammatory properties. However, GCs effect on vocal fold (VF) epithelial morphology and barrier function following injury is overlooked and may be key to efficacy. In this study, the effects of GCs on epithelial morphology and barrier function were quantified in injured VFs. We seek to increase our understanding of biochemical processes underlying GC mechanisms to refine therapeutic strategies.MethodsMicroflap injury was induced in 65 rabbits. Seven days after injury, animals received bilateral 20 μL intracordal injections of saline, dexamethasone, methylprednisolone, or triamcinolone (n = 15 per condition). Five rabbits in each condition were euthanized 1, 7, or 60 days following treatment. An additional five animals served as non‐injured/untreated controls. To quantify transepithelial electrical resistance (TEER), 1 mm epithelial biopsies were placed in an Ussing chamber. The contralateral VF was processed for transmission electron microscopy and epithelial depth analysis.ResultsAt 60 days, GC treatment maintained TEER levels similar to non‐injured/untreated controls. However, triamcinolone reduced TEER compared with saline‐treated conditions. Acutely, epithelial hyperplasia typically persisted in all injured VFs. At 60 days, only dexamethasone and triamcinolone increased epithelial depth in injured VFs; all GCs increased epithelial depth compared with non‐injured/untreated controls.ConclusionAcutely, GCs did not alter TEER. Additionally, GCs did not alter epithelial depth compared with saline treatment, indicating alignment with natural healing responses. At 60 days, GCs exhibited varying degrees of TEER restoration and epithelial hyperplasia, possibly due to distinct pharmacodynamic profiles.Level of EvidenceNA Laryngoscope, 2024
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