Shah Farhan, Forsgren Sture, Holmlund Thorbjörn, Levring Jäghagen Eva, Berggren Diana, Franklin Karl A, Stål Per
Department of Integrative Medical Biology Umeå University Umeå Sweden.
Laboratory of Muscle Biology, the Department of Clinical Sciences, Otolaryngology Umeå University Umeå Sweden.
Laryngoscope Investig Otolaryngol. 2018 Nov 28;4(1):174-180. doi: 10.1002/lio2.225. eCollection 2019 Feb.
Neuromuscular injuries are suggested to contribute to upper airway collapse and swallowing dysfunction in patients with sleep apnea. Neurotrophins, a family of proteins involved in survival, development, and function of neurons, are reported to be upregulated in limb muscle fibers in response to overload and nerve damage. We aimed to investigate the expression of two important neurotrophins, brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), in muscle fibers of uvula from snorers and sleep apnea patients and to compare these findings with pharyngeal function.
Uvula muscle biopsies from 22 patients and 10 controls were analyzed for BDNF, NGF, and cytoskeletal protein desmin using immunohistochemistry. Pharyngeal swallowing function was assessed using videoradiography.
BDNF, but not NGF, was significantly upregulated in a subpopulation of muscle fibers in snoring and sleep apnea patients. Two major immunoreaction patterns for BDNF were observed; a fine grainy point like BDNF staining was displayed in muscle fibers of both patients and controls (41 ± 23 vs. 25 ± 17%, respectively, = .06), while an abnormal upregulated intense-dotted or disorganized reaction was mainly observed in patients (8 ± 8 vs. 2 ± 2%, = .02). The latter fibers, which often displayed an abnormal immunoreaction for desmin, were more frequent in patients with than without swallowing dysfunction (10 ± 8 vs. 3 ± 3%, = .05).
BDNF is upregulated in the upper airway muscles of snorers and sleep apnea patients, and especially in patients with swallowing dysfunction. Upregulation of BDNF is suggested to be a response to denervation, reinnervation, and repair of injured muscle fibers. Our findings propose that damaged upper airway muscles might heal following treatment for snoring and sleep apnea.
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神经肌肉损伤被认为与睡眠呼吸暂停患者的上气道塌陷和吞咽功能障碍有关。神经营养因子是一族参与神经元存活、发育和功能的蛋白质，据报道，在肢体肌肉纤维中，神经营养因子会因负荷过重和神经损伤而上调。我们旨在研究打呼者和睡眠呼吸暂停患者悬雍垂肌纤维中两种重要神经营养因子，即脑源性神经营养因子（BDNF）和神经生长因子（NGF）的表达情况，并将这些结果与咽部功能进行比较。
对22例患者和10例对照者的悬雍垂肌活检组织进行免疫组织化学分析，检测BDNF、NGF和细胞骨架蛋白结蛋白。采用视频荧光造影评估咽部吞咽功能。
打呼者和睡眠呼吸暂停患者的部分肌纤维中BDNF显著上调，而NGF无明显变化。观察到BDNF有两种主要免疫反应模式；患者和对照者的肌纤维中均出现细颗粒状点状BDNF染色（分别为41±23%和25±17%，P=.06），而患者中主要观察到异常上调的密集点状或紊乱反应（8±8%和2±2%，P=.02）。后一种纤维通常对结蛋白有异常免疫反应，在有吞咽功能障碍的患者中比无吞咽功能障碍的患者更常见（10±8%和3±3%，P=.05）。
打呼者和睡眠呼吸暂停患者的上气道肌肉中BDNF上调，尤其是有吞咽功能障碍的患者。BDNF上调被认为是对失神经支配、再支配和受损肌纤维修复的一种反应。我们的研究结果表明，打鼾和睡眠呼吸暂停治疗后受损的上气道肌肉可能会愈合。
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