Abstract: Objective　To comparatively analyze the advantages and disadvantages of three different modeling methods for obstructive sleep apnea (OSA): chronic intermittent hypoxia (CIH), sodium hyaluronate gel injection at the junction of the hard and soft palate (HA-T), and botulinum toxin type A injection into the genioglossus muscle (BoNT-A).Methods　Twenty-four 8-week-old male Sprague Dawley rats were randomly divided into four groups: control, CIH, HA-T, and BoNT-A. Rats in the control group were kept in a normoxic environment. The CIH group underwent daily intermittent hypoxia exposure for 8 hours over 4 weeks. The HA-T group received HA-T injections at the hard-soft palate junction, while the BoNT-A group received BoNT-A injections into the genioglossus muscle, followed by a 4-week observation period. Successful modeling was assessed by monitoring periodic changes in body weight, blood oxygen saturation (SpO2 ) at the end of the 4th week, the maximum distance from the free edge of the soft palate to the trachea, hematoxylin-eosin (HE) staining of left lung tissue, and ELISA detection of blood inflammatory factors.Results　Compared with the control group, the CIH, HA-T, and BoNT-A groups exhibited weight loss. Both the HA-T and BoNT-A groups showed significantly reduced mean SpO2 [HA-T(89.00±2.61)vs. (93.50±1.38), P<0.05], [BoNT A(85.17±4.22)vs. (93.50±1.38), P<0.001]. The BoNT-A group demonstrated a significant narrowing of the maximum distance from the soft palate free edge to the trachea (2.70±0.14) vs. (3.18±0.14), P<0.001. HE staining revealed lung tissue damage in the CIH, HA-T, and BoNT-A groups compared with the control group. ELISA result showed that TNF-α and IL-1β levels were significantly elevated in the CIH group [TNF-α(36.98±5.16) vs. (13.16±1.67), P<0.01], [IL-1β (16.58±1.09) vs. (11.09±1.54), P<0.05, while TNF-α levels were also markedly increased in the BoNT-A group (51.00±7.64) vs. (13.16±1.67), P<0.001. TNF-α levels in the CIH and BoNT-A groups were significantly higher than in the HA-T group [CIH(36.98±5.16) vs. (18.10±4.60), P< 0.05], [BoNT-A(51.00±7.64)vs. (18.10±4.60), P<0.001].Conclusion　All three modeling methods successfully induced OSA-like symptoms in rats, while the BoNT-A group exhibiting the most pronounced upper airway obstruction.

Key words: obstructive sleep apnea, chronic intermittent hypoxia, airway obstruction

摘要： 目的　对比分析慢性间歇性低氧(CIH),在硬腭、软腭交界处注射透明质酸钠凝胶(HA-T),颏舌肌注射A型 肉毒毒素(BoNT-A)3种不同的阻塞性睡眠呼吸暂停(OSA)建模方法的优劣。方法　将24只8周龄雄性SD大鼠 随机分成对照组、CIH组、HA-T组和BoNT-A组。对照组的大鼠置于正常氧浓度环境中;CIH组大鼠则每日接受 8 h的间歇性低氧暴露,持续4周;HA-T组大鼠在硬腭与软腭交界处注射HA-T;BoNT-A组大鼠则在颏舌肌内注射 BoNT-A,并观察4周。通过记录大鼠体质量周期性变化、干预第4周末大鼠血氧饱和度(SpO2 )变化、大鼠软腭游离 缘到气管的最大距离、大鼠左肺组织HE染色及Elisa法检测血液炎症因子等指标判定建模是否成功。结果　与对 照组相比,CIH组、HA-T组及BoNT-A组体质量下降。HA-T组与BoNT-A组大鼠的平均血氧饱和度(MSpO2 )均显 著降低[HA-T(89.00±2.61)vs. (93.50±1.38),P<0.05],[BoNT-A(85.17±4.22)vs. (93.50±1.38),P<0.001]。 BoNT-A组大鼠软腭游离缘到气管的最大距离显著缩窄(2.70±0.14)vs.(3.18±0.14),P<0.001。HE染色结果显 示,与对照组相比,CIH组、HA-T组及BoNT-A组大鼠的左肺组织均出现损伤。Elisa法检测发现与对照组相比, CIH组TNF-α和IL-1β浓度显著升高[TNF-α(36.98±5.16)vs.(13.16±1.67),P<0.01],[IL-1β(16.58±1.09)vs. (11.09±1.54),P<0.05];BoNT-A组TNF-α浓度也明显升高(51.00±7.64)vs. (13.16±1.67),P<0.001。CIH组与 BoNT-A组TNF-α水平较HA-T组显著升高[CIH(36.98±5.16)vs. (18.10±4.60),P<0.05],[BoNT-A(51.00± 7.64)vs.(18.10±4.60),P<0.001]。结论　3种建模方法均成功诱导了大鼠的OSA症状,其中BoNT-A组大鼠的 上气道梗阻表现尤为突出。

关键词: 阻塞性睡眠呼吸暂停, 慢性间歇性低氧, 气道阻塞