慢性间歇性缺氧对大鼠茎突舌肌的影响及作用机制

doi:10.6040/j.issn.1673-3770.0.2024.673

摘要/Abstract

摘要： 目的探讨慢性间歇性缺氧(chronic intermittent hypoxia, CIH)对大鼠茎突舌肌形态结构及收缩功能相关蛋白表达的影响,并分析血清素(5-hydroxytryptamine, 5-HT)在其中的调控作用。方法将30只雄性SD大鼠随机分为常氧对照组和CIH组;CIH组进一步分为3周(3wCIH)、5周(5wCIH)及8周(8wCIH)暴露组.于相应时间点取茎突舌肌组织,采用苏木精-伊红(hematoxylin-eosin, HE)染色观察其形态结构,免疫组织化学法检测5-HT、5-HT 2A受体、兰尼碱受体(ryanodine receptor, RYR)及肌浆网钙ATP酶(sarcoendoplasmic reticulum Ca²⁺-transporting ATPase, SERCA)蛋白表达水平。结果与对照组相比,各CIH组大鼠茎突舌肌出现肌纤维排列紊乱、间距增大及细胞核分布杂乱等形态学改变,且损伤程度随缺氧时间延长而加重。免疫组织化学结果显示,与对照组相比,3wCIH组5-HT(P<0.01)及5-HT 2A受体(P<0.05)表达上调,且高于5wCIH 与8wCIH组,差异有统计学意义(P<0.001);各CIH组(3wCIH、5wCIH、8wCIH)的RYR表达量随时间呈持续下降趋势,差异有统计学意义(P<0.05);SERCA表达量在5wCIH组和8wCIH组降低,差异有统计学意义(P<0.01),总体呈时间依赖性下降趋势。结论长期CIH可导致茎突舌肌结构损伤,伴随5-HT能神经调控的代偿机制失效以及钙调控蛋白表达下调,最终引起收缩功能受损。

关键词: 慢性间歇性缺氧, 茎突舌肌, 血清素

Abstract: Objective To investigate the effects of chronic intermittent hypoxia(CIH)on the morphological structure and expression of contraction-related proteins in the styloglossus muscle of rats, and to analyze the regulatory role of serotonin(5-hydroxytryptamine, 5-HT)in this process. Methods Thirty male Sprague Dawley(SD)rats were randomly divided into a normoxic control group and a CIH group, which was further subdivided into 3-week(3wCIH), 5-week(5wCIH), and 8-week(8wCIH)exposure groups. At the respective time points, styloglossus muscle tissues were collected, hematoxylin-eosin(HE)staining was used to observe their morphological structure, and immunohistochemistry was employed to detect the protein expression levels of 5-HT, 5-HT 2A receptor, ryanodine receptor(RYR), and sarcoplasmic reticulum Ca²⁺-transporting ATPase(SERCA). Results Compared with the control group, the rats in each CIH group exhibited morphological changes in the styloglossus muscle, such as disordered muscle fiber arrangement, increased spacing, and chaotic distribution of cell nuclei, with the severity of damage increasing with prolonged hypoxia. Immunohistochemical results showed that compared with the control group, the expression of 5-HT(P<0.01)and 5-HT 2A receptor(P<0.05)was upregulated in the 3wCIH group, and was higher than that in the 5wCIH and 8wCIH groups, with statistically significant differences(P<0.001). The expression of RYR in each CIH group(3wCIH, 5wCIH, 8wCIH)showed a continuous downward trend over time, with statistically significant differences(P<0.05). The expression of SERCA decreased in the 5wCIH and 8wCIH groups, with statistically significant differences(P<0.01), showing an overall time-dependent downward trend. Conclusion Long-term CIH can lead to structural damage to the styloglossus muscle, accompanied by the failure of the compensatory mechanism regulated by 5-HTergic nerves and downregulation of calcium-regulatory protein expression, ultimately causing impaired contraction function.

Key words: Chronic intermittent hypoxia, Styloglossus muscle, 5-hydroxytryptamine

中图分类号:

吉睿,刘雅洁,王佳琪,史雅文,张炜明,殷敏. 慢性间歇性缺氧对大鼠茎突舌肌的影响及作用机制[J]. 山东大学耳鼻喉眼学报, 2026, 40(2): 44-48.

JI Rui, LIU Yajie, WANG Jiaqi, SHI Yawen, ZHANG Weiming, YIN Min. The effects of chronic intermittent hypoxia on the styloglossus muscle in rats and its mechanism of action[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2026, 40(2): 44-48.

参考文献

[1] Witkowska A, Jaromirska J, Gabryelska A, et al. Obstructive sleep apnea and serotoninergic signalling pathway: pathomechanism and therapeutic potential[J]. Int J Mol Sci, 2024, 25(17): 9427. doi:10.3390/ijms25179427
[2] Rukhadze I, Fenik VB, Benincasa KE, et al. Chronic intermittent hypoxia alters density of aminergic terminals and receptors in the hypoglossal motor nucleus[J]. Am J Respir Crit Care Med, 2010, 182(10): 1321-1329
[3] Fleury Curado T, Oliven A, Sennes LU, et al. Neurostimulation treatment of OSA[J]. Chest, 2018, 154(6): 1435-1447
[4] Mateika JH, Millrood DL, Kim J, et al. Response of human tongue protrudor and retractors to hypoxia and hypercapnia[J]. Am J Respir Crit Care Med, 1999, 160(6): 1976-1982
[5] Fuller DD, Williams JS, Janssen PL, et al. Effect of co-activation of tongue protrudor and retractor muscles on tongue movements and pharyngeal airflow mechanics in the rat[J]. J Physiol, 1999, 519(Pt 2): 601-613
[6] 薛荣, 张希龙. 咽部肌肉和结构与阻塞性睡眠呼吸暂停的关系[J]. 山东大学耳鼻喉眼学报, 2016, 30(5): 9-12 XUE Rong, ZHANG Xilong. Relationship between obstructive sleep apnea and pharyngeal muscles and structure[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2016, 30(5): 9-12
[7] Kubin L. Neural control of the upper airway: respiratory and state-dependent mechanisms [J]. Compr Physiol. 2016, 6(4): 1801-1850
[8] Lipford MC, Ramar K, Liang YJ, et al. Serotnin as a possible biomarker in obstructive sleep apnea[J]. Sleep Med Rev, 2016, 28: 125-132. doi:10.1016/j.smrv.2015.08.003
[9] 刘雅洁, 王欢欢, 张钦鑫, 等. CIH所致颏舌肌功能改变中5-HT调控作用的初步研究[J]. 中国中西医结合耳鼻咽喉科杂志, 2021, 29(4): 246-251 LIU Yajie, WANG Huanhuan, ZHANG Qinxin, et al. A preliminary study on the role of 5-HT in regulating genioglossus muscle function induced by CIH[J]. Chinese Journal of Otorhinolaryngology in Integrative Medicine, 2021, 29(4): 246-251
[10] Dotan Y, Pillar G, Schwartz AR, et al. Asynchrony of lingual muscle recruitment during sleep in obstructive sleep apnea[J]. J Appl Physiol, 2015, 118(12): 1516-1524
[11] Si L, Zhang J, Wang Y, et al. Obstructive sleep apnea and respiratory center regulation abnormality[J]. Sleep Breath, 2021, 25(2): 563-570
[12] Sutlive TG, Shall MS, McClung JR, et al. Contractile properties of the tongue's genioglossus muscle and motor units in the rat[J]. Muscle Nerve, 2000, 23(3): 416-425
[13] Huang HP, Zhang XF, Ding N, et al. Effects of chronic intermittent hypoxia on genioglossus in rats[J]. Sleep Breath, 2012, 16(2): 505-510
[14] Oliven R, Cohen G, Somri M, et al. Spectral analysis of peri-pharyngeal muscles' EMG in patients with OSA and healthy subjects[J]. Respir Physiol Neurobiol, 2019, 260: 53-57. doi:10.1016/j.resp.2018.12.002
[15] Oliven R, Cohen G, Somri M, et al. Peri-pharyngeal muscle response to inspiratory loading: comparison of patients with OSA and healthy subjects[J]. J Sleep Res, 2019, 28(5): e12756. doi:10.1111/jsr.12756
[16] Oliven R, Cohen G, Somri M, et al. Relationship between the activity of the genioglossus, other peri-pharyngeal muscles and flow mechanics during wakefulness and sleep in patients with OSA and healthy subjects[J]. Respir Physiol Neurobiol, 2020, 274: 103362. doi:10.1016/j.resp.2019.103362
[17] Meng YL, Li WY, Zou Y, et al. How does chronic intermittent hypoxia influence upper airway stability in rats?[J]. Nat Sci Sleep, 2020, 12: 749-758. doi:10.2147/nss.s249948
[18] Cao R, Zhang MJ, Zhou YT, et al. The dorsal and the ventral side of hypoglossal motor nucleus showed different response to chronic intermittent hypoxia in rats[J]. Sleep Breath, 2021, 25(1): 325-330
[19] Mateika JH, Sandhu KS. Experimental protocols and preparations to study respiratory long term facilitation[J]. Respir Physiol Neurobiol, 2011, 176(1/2): 1-11
[20] Dunleavy M, Bradford A, O'Halloran KD. Oxidative stress impairs upper airway muscle endurance in an animal model of sleep-disordered breathing[J]. Adv Exp Med Biol, 2008, 605: 458-462. doi:10.1007/978-0-387-73693-8_80
[21] Skelly JR, Edge D, Shortt CM, et al. Tempol ameliorates pharyngeal dilator muscle dysfunction in a rodent model of chronic intermittent hypoxia[J]. Am J Respir Cell Mol Biol, 2012, 46(2): 139-148
[22] Avila G, de la Rosa JA, Monsalvo-Villegas A, et al. Ca²⁺ channels mediate bidirectional signaling between sarcolemma and sarcoplasmic reticulum in muscle cells[J]. Cells, 2019, 9(1): 55. doi:10.3390/cells9010055
[23] Liu YH, Li W, Song WH. Effects of oestrogen on sarcoplasmic reticulum Ca²⁺-ATPase activity and gene expression in genioglossus in chronic intermittent hypoxia rat[J]. Arch Oral Biol, 2009, 54(4): 322-328

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