阻塞性睡眠呼吸暂停低通气综合征患者咽腔内压力变化对上气道扩张肌功能的影响机制

项目来源

国家自然科学基金(NSFC)

项目主持人

叶京英

项目受资助机构

清华大学

立项年度

2016

立项时间

未公开

项目编号

81670918

研究期限

未知 / 未知

项目级别

国家级

受资助金额

60.00万元

学科

医学科学-耳鼻咽喉头颈科学-咽喉及颈部疾病

学科代码

H-H14-H1402

基金类别

面上项目

关键词

咽腔 ; 颏舌肌 ; 压力 ; 睡眠呼吸暂停 ; 阻塞性 ; genioglossus ; obstructive ; sleep apnea ; pharyngeal cavity ; pressure

参与者

尹国平;张欢;顼晋昆;胡斌;张玉焕;曲玥;李京京;李琨;郭文佳

参与机构

清华大学

项目标书摘要:上气道扩张肌功能障碍目前被认为是阻塞性睡眠呼吸暂停低通气综合征(OSAHS)核心的发生机制。上气道扩张肌的激活,对于维持睡眠时气道的开放起重要作用。睡眠呼吸暂停发生时呼吸驱动下降,造成上气道扩张肌张力和咽腔负压平衡出现失调。研究提示,咽腔内压力变化的刺激可以通过呼吸中枢对上气道扩张肌进行反馈调控。说明咽腔粘膜的感觉传入功能可能与OSAHS神经肌肉方面的发病机制相关。为证实该假设,本研究在既往研究的基础上,通过定量改变咽腔内部压力,观察睡眠时颏舌肌肌电的变化规律,了解咽部压力刺激变化对上气道扩张肌功能的影响。并进一步在动物模型上,观察不同咽腔压力下颏舌肌肌电在咽部粘膜表面麻醉与非麻醉阻滞组之间的差异,阐明咽腔粘膜感受器在上气道扩张肌活性调控中的作用。阐明上述问题将为深入认识OSAHS神经肌肉调控机制,寻找新的治疗靶点提供理论依据。

Application Abstract: The key pathogenesis of obstructive sleep apnea-hypopnea syndrome(OSAHS)are now recognized as upper airway(UA)dilators dysfunction.The activation of the UA dilators may play an important role to restore pharyngeal patency.Sleep apnea occurs during the low respiratory drive period,and the balance of UA dilators activity and pharyngeal airway negative pressure appears disorders.Recent studies confirmed that the UA dilators can be regulated by the activation of the respiratory drive center via the sensory afferent pathway initiated by the change of pharyngeal pressure.It is believed that the afferent function of pharyngeal mucosa may be closely related to the neuromuscular pathogenesis of OSAHS.Based on the previous studies,we want to observe the variation of genioglossus electromyography following alteration of upper airway pressure to make sure the effects of pharyngeal pressure on genioglossus activity.Further to observe genioglossus activity under different negative airway pressure in animal model with or without mucosa anaesthesia blocked,in order to clarify the role of pharyngeal mucosa receptor in the pathway of genioglossus feedback control.Clarifying these issues could help us to get in-depth understanding of OSAHS neuromuscular control mechanism and provide a theoretical basis for new therapeutic options.

项目受资助省

北京市

项目结题报告(全文)

上气道扩张肌功能障碍目前被认为是阻塞性睡眠呼吸暂停低通气综合征(OSAHS)核心的发病机制。上气道扩张肌的激活,对于维持睡眠时气道的开放起重要作用。睡眠呼吸暂停发生时呼吸驱动下降,造成上气道扩张肌张力和咽腔负压平衡出现失调。本研究完成了不同咽腔压力变化下成人睡眠监测同步口内颏舌肌肌电(GGEMG)测量的研究工作,通过定量改变咽腔内部压力,观察睡眠时颏舌肌肌电的变化规律,了解咽部压力刺激变化对上气道扩张肌功能的影响;同时分析了OSAHS患者清醒及睡眠期GGEMG各参数的特征以及应用CPAP治疗前后OSAHS患者颏舌肌肌电活性变化特点;此外,对睡眠初始GGEMG与改良腭咽成形术(H-UPPP)的手术疗效进行了相关性分析。主要结论如下:1)无论在清醒期还是NREM期,OSAHS患者均存在GGEMG的高活性表现;2)OSAHS患者可因为睡眠期频繁呼吸事件而导致GGEMG的过度反应,从而加重GG的神经肌肉损伤和肌肉收缩疲劳,不利于代偿性活动的维持;3)对OSAHS患者应用经鼻CPAP可消除呼吸事件并维持气道稳定性,具有GG活性的保护性作用,并推测可预防永久性GG神经肌肉损害;4)OSAHS患者入睡初期颏舌肌平均肌电值可预测腭咽部手术疗效,入睡后颏舌肌肌电活性较高的患者可能更适合接受手术治疗。

  • 排序方式:
  • 2
  • /
  • 1.Chronic intermittent hypoxia induces cognitive impairment in Alzheimer's disease mouse model via postsynaptic mechanisms.

    • 关键词:
    • Alzheimers disease; Chronic intermittent hypoxia; Cognition; Obstructive sleep apnea; Synaptic plasticity
    • Li, Juan;Ye, Jingying
    • 《Sleep & breathing = Schlaf & Atmung》
    • 2024年
    • 期刊

    PURPOSE: Obstructive sleep apnea (OSA) is highly comorbid with Alzheimer's disease (AD) and may represent a risk factor for inducing or accelerating cognitive impairment in AD. Chronic intermittent hypoxia (CIH) has beenconsidered to be a predictor of developing cognitive decline and AD. However, the precise underlying mechanisms by which CIH contributes to cognitive impairment remain unknown. In the present study, we examined the effects of CIH on cognition and hippocampal function in APP/PS1 mice, an animal model of AD.; METHODS: Wild-type (WT) and APP/PS1 mice were subjected to one of the following conditions for 2weeks: (1) sham condition (continuous room air) or (2) CIH condition. The oxygen concentration of the CIH condition transitioned from 5 to 21%. Behavioral tests, electrophysiological recording, real-time polymerase chain reaction, and Western blot were used to assess the effect of CIHon cognitive performance and synaptic plasticity.; RESULTS: CIH exposure did not affect motor coordination, general locomotor activity, anxiety, or willingnessto explore. However, behavioral test results indicated that APP/PS1-CIH mice showed more spatial learning and memory deficits. CIH induced long-term potentiation (LTP) dysfunction of thehippocampusin WT mice. These effects were aggravated in APP/PS1 mice. The N-methyl-D-aspartic acid receptor (NMDAR) NR1 subunit and postsynaptic density 95 (PSD95) in the hippocampus of WT and APP/PS1 mice were downregulated.; CONCLUSIONS: These findings showed that a postsynaptic mechanism was involved in the effect of CIH on cognitive impairment. © 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

    ...
  • 3.The association between the levels of autoimmune related indicators and clinical condition in sudden deafness patients

    • 关键词:
    • Sudden deafness (SD); typing; antinuclear antibody; anticardiolipinantibody IgG; anticardiolipin antibody IgM;HEARING-LOSS
    • Li, Xin;Chen, Wenjing;Yi, Haijin;Xu, Jia;Lu, Manlin;Guo, Feifei;Li, Xiaochen;Ye, Jingying
    • 《ANNALS OF PALLIATIVE MEDICINE》
    • 2021年
    • 10卷
    • 10期
    • 期刊

    Background: This study aimed to analyze the abnormal rates of immune related factors in serum of sudden deafness (SD) patients, and to discuss the correlation between these indicators and the degree of pathological changes of SD patients.Methods: From March 2018 to January 2021, 90 patients with SD who were hospitalized in Beijing Tsinghua Changgeng Hospital were enrolled as participants, and 60 healthy examinees served as the control group. Antinuclear antibody (ANA), anticardiolipin antibody immunoglobulin G (ACA-IgG), anticardiolipin antibody immunoglobulin M (ACA-IgM), and anti-beta-glucoprotein (anti-beta-GP) antibody were detected by enzyme-linked immunosorbent assay (ELISA).Results: In the SD group, 43 participants were positive for ANA, while in the control group, only 9 participants were positive for ANA. The titer of antibodies was significantly higher in the SD group than in the control group. The differences in abnormal rates of ACA-IgG, ACA-IgM, and anti-beta-GP antibodies between the SD group and control group were not statistically significant (P>0.05).Conclusions: The pathogenesis of SD is correlated with autoimmune factors to a certain extent. In the course of clinical treatment, in addition to vasodilation, neurotrophic therapy, and thrombolytic therapy, patients can also be approached from the perspective of autoimmunity, which may achieve more ideal treatment effects.

    ...
  • 4.Analysis of the myoelectric characteristics of genioglossus in REM sleep and its improvement by CPAP treatment in OSA patients.

    • 关键词:
    • Continuous positive airway pressure; Genioglossus; Intra-oral surface electrode; Neuromuscular lesions; Obstructive sleep apnea
    • Zhou, Yingqian;Zhao, Di;Yin, Guoping;Li, Jingjing;Cao, Xin;Zhang, Yuhuan;Ye, Jingying
    • 《Sleep & breathing = Schlaf & Atmung》
    • 2020年
    • 24卷
    • 2期
    • 期刊

    OBJECTIVES: To reveal the characteristics of genioglossus (GG) activation in moderate and severe obstructive sleep apnea (OSA) patients during rapid eye movement (REM) sleep compared with non-rapid eye movement (NREM) sleep and to determine whether continuous positive airway pressure (CPAP) could improve GG activation in OSA patients during sleep.; METHODS: All subjects underwent polysomnography (PSG) with synchronous GG electromyography (GGEMG) recording with intra-oral surface electrodes at baseline on the first night. Only those subjects diagnosed with moderate and severe OSA were included and were manually titrated with CPAP to achieve a therapeutic pressure (Pt) with GGEMG recording on the second night.; RESULTS: Nine OSA patients and six normal controls were analyzed in this study. The tonic GGEMG was higher in OSA patients during wakefulness (p=0.003) and NREM sleep (p=0.015), but it was not higher in REM sleep (p=0.862). The average phasic activity of OSA patients was significantly higher in all stages, including wakefulness (p=0.007), NREM sleep (p=0.005), and REM sleep (p=0.021). The peak phasic GGEMG was not different in wakefulness compared with normal controls (p=0.240), but it was higher in OSA patients in NREM sleep (p=0.001) and REM sleep (p=0.021), and it was significantly reduced by using CPAP during sleep (NREM sleep: p=0.027; REM sleep: p=0.001).; CONCLUSIONS: Our results demonstrate that GG activation during NREM and REM sleep is associated with component differences. The tonic component of GGEMG exhibited less of a compensatory increase compared with the phasic component in REM sleep, suggesting that it may be one of the pathological mechanisms of UA collapsibility in REM sleep. In addition, treatment with CPAP can normalize GGEMG activity and mostly reduced the peak phasic GGEMG during sleep.

    ...
  • 5.Five-Year Objective and Subjective Outcomes of Velopharyngeal Surgery for Patients with Obstructive Sleep Apnea

    • 关键词:
    • obstructive sleep apnea; velopharyngeal surgery; polysomnography;Epworth Sleep Scale;FOLLOW-UP; UPPER AIRWAY; SURGICAL MODIFICATIONS; COST-EFFECTIVENESS;UVULOPALATOPHARYNGOPLASTY; COMBINATION; PHYSIOLOGY; ANATOMY; OSA
    • Yin, Guoping;He, Mu;Cao, Xin;Xu, Jinkun;Zhang, Yuhuan;Kang, Dan;Ye, Jingying
    • 《OTOLARYNGOLOGY-HEAD AND NECK SURGERY》
    • 2019年
    • 162卷
    • 1期
    • 期刊

    Objective To assess the long-term effects of velopharyngeal surgery on objective and subjective symptoms in patients with obstructive sleep apnea (OSA). Study Design Prospective cohort study. Setting University medical center. Subjects and Methods Eighty-six patients with OSA underwent velopharyngeal surgery, which consisted of revised uvulopalatopharyngoplasty with uvula preservation, with or without concomitant transpalatal advancement pharyngoplasty. The results from polysomnography and the Epworth Sleep Scale after 6 months and 5 years were compared with baseline. Baseline variables were compared between responders and nonresponders. Results Sixty-three patients were successfully followed up at the end of study. The surgical success rate after 6 months and 5 years was 66.67% (42 of 63) and 60.32% (38 of 63), respectively, with no significant difference (P = .459). The apnea-hypopnea index and Epworth Sleep Scale dramatically decreased from baseline after 6 months and 5 years in responders and nonresponders (P < .001 for all). As compared with nonresponders, the responders exhibited larger tonsil size, higher nocturnal lowest oxygen desaturation, lower CT90 (percentage of time with oxygen saturation <90%), and shorter MH (vertical distance between the lower edge of the mandible and hyoid in the midsagittal plane of computed tomography). Tonsil size and CT90 showed significant predictive value for surgery success (P < .001 for both). Conclusion Velopharyngeal surgery was effective in improving nocturnal respiration and excessive daytime sleepiness in patients with OSA at 6-month and 5-year follow-up. Tonsil size and CT90 could be predictors for surgery responders.

    ...
  • 6.The Role of Genioglossus Activity in Predicting Uvulopalatopharyngoplasty Outcomes

    • 关键词:
    • obstructive sleep apnea; genioglossus activity; tonsil size;uvulopalatopharyngoplasty;OBSTRUCTIVE SLEEP-APNEA; UPPER AIRWAY; COLLAPSIBILITY; ACTIVATION
    • Zhao, Di;Li, Yanru;Qu, Yue;Zhang, Junbo;Cao, Xin;Ye, Jingying
    • 《OTOLARYNGOLOGY-HEAD AND NECK SURGERY》
    • 2019年
    • 162卷
    • 2期
    • 期刊

    Objective The aim of this study was to evaluate the association between genioglossus activity during sleep onset and the outcome of uvulopalatopharyngoplasty (UPPP) in patients with obstructive sleep apnea. Study Design Case series with planned data collection. Setting Sleep medical center. Subjects and Methods Forty-four patients with obstructive sleep apnea underwent overnight polysomnography with synchronous genioglossus electromyography (GGEMG) with intraoral electrodes. In addition, all patients underwent revised UPPP with uvula preservation and were followed up with polysomnography at least 3 months after surgery. Results Twenty-five patients (56.8%) were responders. Multiple regression analysis revealed that increasing tonsil size (odds ratio [OR], 0.086; P = .038) and higher sleep-onset GGEMG (OR, 0.664; P = .04) were significant predictors for surgical success. The area under the receiver operating characteristic curve was 0.942 (OR, 0.040; P < .001) for those predictors, 0.884 for GGEMG, and 0.848 for tonsil size. Moreover, all patients were divided into 4 groups according to tonsil size and sleep-onset GGEMG. The success rate of patients with tonsil size III or IV and sleep-onset GGEMG >11.20% (maximal GGEMG) was optimal (92.9%, 13 of 14), while the success rate of patients with tonsil size I or II and sleep-onset GGEMG <= 11.20% was 0% (0 of 10). Conclusions Sleep-onset GGEMG and tonsil size are both important in deciding outcomes of UPPP. Patients with tonsil size III or IV and higher sleep onset may be more suitable candidates for UPPP because of the higher probability of surgical success.

    ...
  • 7.不同年龄眩晕患者OSAHS构成比的相关性分析

    • 关键词:
    • 眩晕;阻塞性睡眠呼吸暂停低通气综合征;睡眠呼吸指数;构成比;相关性
    • 李欣;陈雯婧;李娟;张玉焕;梁思超;郭振平;卢曼林;孙宇;袁雪梅;渠莉芬;陈强;叶京英
    • 《中华耳科学杂志》
    • 2020年
    • 02期
    • 期刊

    目的调查分析不同年龄段眩晕患者的诊断及发生阻塞性睡眠呼吸暂停低通气综合征(OSAHS)的构成比。方法 201例以眩晕为主诉的患者分别发放睡眠问卷和平衡问卷,包括Epworth量表、STOP-Bang量表和DHI量表。完成前庭双温试验、位置试验、耳蜗电图检查(EochG)、前庭肌源诱发电位(VEMP)检查多导睡眠监测(PSG)检查。同时向社区居民中,正常无症状人群发放同样问卷量表。从问卷完全正常且无其它病史的人群中选择40例志愿者,从未发作眩晕者作对照组,且对照组的性别年龄及BMI与眩晕患者组匹配数据无差异,并完成同样上述检查。结果 201例患者PSG检查结果96例有睡眠呼吸指数(AHI)异常。轻、中、重、度的OSAHS构成比分别为22.9%、11.9%、12.9%,。90例患者最低血氧饱和度低于正常值,轻、中、重、度比例分别为26.9%、8.5%、9.5%。睡眠异常问卷量表得分与BMI、AHI、血氧、STOP-Bang量表得分均有相关性,DHI量表得分与年龄和STOP-Bang量表得分有相关性。正常人40名志愿者中,OSAHS及DHI得分与年龄无相关性。患者组中的患有OSAHS构成比较对照组高,有统计学意义(P=0.044)。结论本研究中眩晕患者占OSAHS的构成比为47.8%。最低血氧饱和度异常所占构成比为44.8%,均高于正常对照组。

    ...
  • 8.持续气道正压通气治疗对纠正中-重度阻塞性睡眠呼吸暂停患者颏舌肌肌电过高活性反应的评估

    • 关键词:
    • 睡眠呼吸暂停;阻塞性;持续气道正压通气;颏舌肌;口内表面电极
    • 周颖倩;赵迪;尹国平;李京京;曹鑫;张玉焕;叶京英
    • 《中华耳鼻咽喉头颈外科杂志》
    • 2019年
    • 8期
    • 期刊

    目的分析比较持续气道正压通气(CPAP)治疗前后中-重度阻塞性睡眠呼吸暂停(OSA)患者颏舌肌肌电值(GGEMG)的差异.方法对2016年8月至2017年9月在北京清华长庚医院耳鼻咽喉头颈外科睡眠中心的打鼾男性患者和无打鼾男性健康志愿者进行整夜多

    ...
  • 9.[Effectiveness of continuous positive airway pressure ventilation in improving genioglossus electromyography in patients with moderate to severe obstructive sleep apnea].

    • 关键词:
    • Continuous positive airway pressure; Genioglossus; Intraoral electrode; Sleep apnea, obstructive
    • Zhou, Y Q;Zhao, D;Yin, G P;Li, J J;Cao, X;Zhang, Y H;Ye, J Y
    • 《Zhonghua er bi yan hou tou jing wai ke za zhi = Chinese journal of otorhinolaryngology head and neck surgery》
    • 2019年
    • 54卷
    • 8期
    • 期刊

    Objective: To compare the changes of genioglossus electromyography (GGEMG) with and without continuous positive airway pressure (CPAP) ventilation in moderate to severe obstructive sleep apnea (OSA) patients. Methods: Each of subjects, including male snorers and non-snorers, underwent polysomnography (PSG) with synchronous GGEMG recording with intra-oral bipolar silver ball electrodes at the Sleep Center of Beijing Tsinghua Changgung Hospital from August 2016 to Sepember 2017. Manual CPAP pressure titration and with GGEMG were performed in patients diagnosed moderate to severe OSA. T-test was used to compare the changes of GGEMG in OSA group (n=12, AHI (65.90+23.67) events/h) and control group (n=6, AHI(2.30+1.93) events/h) before and after CPAP treatment. Results: Variables of GGEMG (including tonic, peak and phasic GGEMG) were higher in OSA group than in control group during both wakefulness and non rapid eye movement(NREM) sleep. However, with CPAP treatment, the GGEMG variables were significantly decreased in OSA group during NREM sleep(tonic GGEMG: 1.23%±0.73% vs. 2.54%±1.12%, t=4.024, P=0.002; peak GGEMG: 12.37%±13.19% vs. 26.98%±15.52%, t=2.795, P=0.017; phasic GGEMG: 3.81%±2.47% vs. 8.82%±3.84%, t=5.113, P<0.001). Conclusions: CPAP treatment can eliminate respiratory events and maintain airway patency. It is helpful to normalize the excessive GGEMG response in OSA patients during sleep, which has therapeutic significance to alleviate and prevent genioglossal neuromuscular lesions.

    ...
  • 10.[The effect of genioglossus activity to velopharyngeal surgery in patient with obstructive sleep apnea hypopnea syndrome].

    • 关键词:
    • Genioglossus; Intraoral electrodes; Otorhinolaryngologic surgical procedures; Sleep apnea,obstructive; Velopharyngeal surgery
    • Zhao, D;Li, Y R;Qu, Y;Xian, J F;Cao, X;Zhang, J B;Ye, J Y
    • 《Zhonghua er bi yan hou tou jing wai ke za zhi = Chinese journal of otorhinolaryngology head and neck surgery》
    • 2019年
    • 54卷
    • 6期
    • 期刊

    Objective: To investigate the effect of genioglossus (GG) activation at sleep onset on the outcome of velopharyngeal surgery in obstructive sleep apnea hypopnea syndrome (OSAHS) patients. Methods: Thirty-five patients between April 2014 and February 2015 in Beijing Tongren Hospital with OSAHS underwent overnight polysomnography with synchronous genioglossus electromyography (GGEMG) using intraoral electrodes. The upper airway (UA) anatomy was evaluated by three-dimensional computer tomography (3D-CT) in OSAHS patients. Then, all of the patients received velopharyngeal surgery, including revised uvulopalatopharyngoplasty (UPPP) with uvula preservation or UPPP combined transpalatal advancement pharyngoplasty. All patients were followed-up using polysomnography 3-6 months after surgery. T-test or Wilcoxon test were used to compare the variables between groups, and Spearman correlation analysis was used to test the correlation between parameters. Results: Thirty-five patients received velopharyngeal surgery. Twenty-two patients (62.86%) were responders, and 13 patients (37.14%) were non-responders. Responders had a higher mean GGEMG during sleep onset (15.31±3.74 vs. 9.92±2.93, t=4.504, P=0.001). The decreased AHI was significantly positively related to the sleep onset mean GGEMG (r=0.541, P=0.004) and the change in GGEMG (r=0.422, P=0.028). The decreased AHI was significantly negatively related to the minimal cross sectional airway area (mCSA,rho=0.629,P=0.000) and the minimal lateral airway dimension (mLAT, rho=0.484, P=0.009) at velopharynx. Conclusions: The outcome of velopharyngeal surgery was affected by the mean GGEMG during sleep onset. We speculated that the patient with higher GGEMG at sleep onset and narrower velopharynx were more suitable candidates for velopharyngeal surgery.

    ...
  • 排序方式:
  • 2
  • /