慢性失眠共病OSAHS患者血清NLRP3炎症小体、IL-1β、IL-18水平与睡眠质量、认知功能的相关性研究

Clinical characteristics of sleep quality and cognitive function in patients with chronic insomnia co-morbid OSAHS and their correlation with serum NLRP3 inflammatory vesicles, IL-1β, and IL-18 levels

摘要:

目的 探讨慢性失眠共病阻塞性睡眠呼吸暂停低通气综合征（OSAHS）患者睡眠质量和认知功能的临床特征及其与血清核苷酸结合寡聚化结构域样受体蛋白3（NLRP3）炎症小体、白细胞介素-1β（IL-1β）、白细胞介素-18（IL-18）水平的相关性。方法 选取2021年1月—2022年5月内蒙古科技大学包头医学院第一附属医院114例慢性失眠患者为研究对象，依据多导睡眠监测（PSG）结果将患者分为慢性失眠组58例，慢性失眠共病OSAHS组56例，并选取同期该院健康体检者52例作为对照组。采用匹兹堡睡眠质量指数（PSQI）和PSG评估受试者的睡眠质量，采用蒙特利尔认知评估量表（MoCA）评估总体认知功能，采用酶联免疫吸附试验（ELISA）检测受试者血清NLRP3炎症小体、IL-1β及IL-18水平。Pearson法分析慢性失眠共病OSAHS患者血清NLRP3炎症小体、IL-1β、IL-18水平与睡眠质量、认知功能的相关性。多元线性回归分析慢性失眠共病OSAHS患者睡眠质量和认知功能的影响因素。结果 与慢性失眠组比较，慢性失眠共病OSAHS组患者入睡潜伏期、阻塞性呼吸暂停最长持续时间延长（P <0.05），呼吸暂停低通气指数（AHI）升高（P <0.05），鼾声事件次数增加（P <0.05），非快速眼球运动睡眠1期所占睡眠总时间的百分比（N1%）、快速眼球运动期睡眠所占睡眠总时间的百分比（REM%）、血氧饱和度<90%时间占监测总时间的百分比（TS90%）升高（P <0.05），非快速眼球运动睡眠2期所占睡眠总时间的百分比（N2%）、平均氧饱和度（SpO₂）及最低SpO₂降低（P <0.05）；与对照组比较，慢性失眠共病OSAHS组患者总睡眠时间缩短（P <0.05），入睡潜伏期、睡后觉醒总时间和阻塞性呼吸暂停最长持续时间延长（P <0.05），觉醒次数、AHI及鼾声事件次数增加（P <0.05），PSQI评分、N1%、TS90%升高（P <0.05），睡眠效率、N2%、N3%、平均SpO₂及最低SpO₂降低（P <0.05）。与慢性失眠组比较，慢性失眠共病OSAHS组患者注意力、视空间与执行能力、定向力和MoCA总分降低（P <0.05）；与对照组比较，慢性失眠共病OSAHS组患者注意力、视空间与执行能力、延迟回忆能力、定向力和MoCA总分降低（P <0.05）。慢性失眠共病OSAHS组、慢性失眠组及对照组血清NLRP3炎症小体、IL-1β、IL-18水平分别依次下降（P <0.05）。慢性失眠共病OSAHS组患者Pearson相关性分析结果显示：血清NLRP3炎症小体、IL-1β、IL-18水平与PSQI评分、睡后觉醒总时间、N1%o及AHI呈正相关（P <0.05），与总睡眠时间、TS90%、视空间与执行能力、延迟回忆能力及MoCA总分呈负相关（P <0.05）；IL-1β、IL-18水平与N3%呈负相关（P <0.05）；NLRP3炎症小体、IL-18水平与注意力呈负相关（P <0.05）。多元线性回归分析结果显示：血清NLRP3炎症小体水平影响PSQI评分、N1%、N3%、AHI、TS90%及注意力，IL-1β水平影响PSQI评分、N1%、N3%、TS90%、注意力及延迟回忆能力，IL-18水平影响AHI、TS90%及延迟回忆能力（P <0.05）。结论 慢性失眠共病OSAHS患者的血清NLRP3炎症小体、IL-1β及IL-18水平较慢性失眠患者和正常人高，并且升高的血清NLRP3炎症小体、IL-1β及IL-18与睡眠质量下降、认知功能受损相关。

Abstract:

Objective To investigate the clinical characteristics of sleep quality and cognitive function in patients with chronic insomnia co-morbid obstructive sleep apnea hypopnea syndrome (OSAHS) and its correlation study with serum nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammatory vesicles, interleukin-1β (IL-1β), and interleukin-18 (IL-18) levels.Methods One hundred and fourteen patients with chronic insomnia from January 2021 to May 2022 at the First Affiliated Hospital of Baotou Medical College of Inner Mongolia University of Science and Technology were selected for the study, and were divided into 58 cases of chronic insomnia group and 56 cases of chronic insomnia co-morbid OSAHS group by polysomnography (PSG) monitoring results, and 52 cases of health check-ups at the hospital were collected as the control group during the same period. The subjects' sleep quality was assessed using the Pittsburgh Sleep Quality Index Inventory (PSQI), PSG monitoring, and overall cognitive function was assessed using the Montreal Cognitive Assessment Scale (MoCA), and serum NLRP3 inflammatory vesicles, IL-1β and IL-18 levels were measured by enzyme-linked immunosorbent assay (ELISA). Pearson's method to analyze the correlation between serum NLRP3 inflammatory vesicles, IL-1β and IL-18 levels and sleep quality and cognitive function in patients with chronic insomnia co-morbid OSAHS. Multiple linear regression analysis of factors influencing sleep quality and cognitive function in patients with chronic insomnia co-morbid OSAHS.Results Compared with the chronic insomnia group, patients in the chronic insomnia co-morbid OSAHS group had a significantly longer sleep latency, a longer maximum duration of obstructive apnea (P < 0.05), a higher apnea hypoventilation index (AHI) (P < 0.05), a significantly higher number of snoring events (P < 0.05), a significantly higher percentage of total sleep time accounted for by non-rapid eye movement sleep stage 1 (N1%), a significantly higher percentage of total sleep time accounted for by rapid eye movement sleep as a percentage of total sleep time (REM%), and oxygen saturation < 90% of total monitored time (TS90%) were significantly higher (P < 0.05), and the percentage of non-rapid eye movement sleep 2 as a percentage of total sleep time (N2%), mean oxygen saturation (SpO₂) and minimum SpO₂ were significantly lower (P < 0.05); compared with the control group, patients in the chronic insomnia co-morbid OSAHS group had significantly shorter total sleep time (P < 0.05), significantly longer sleep latency, total post-sleep awakening time and maximum duration of obstructive apnea (P < 0.05), significantly higher number of awakenings, AHI and snoring events (P < 0.05), significantly higher PSQI score, N1%, TS90% (P < 0.05), and significantly lower sleep efficiency, N2%, N3%, mean SpO₂ and minimum SpO₂ (P < 0.05). Patients in the chronic insomnia co-morbid OSAHS group had significantly lower attention, visuospatial and executive ability, orientation and total MoCA scores compared with the chronic insomnia group (P < 0.05); patients in the chronic insomnia co-morbid OSAHS group had significantly lower attention, visuospatial and executive ability, delayed recall, orientation and total MoCA scores compared with the control group (P < 0.05). Serum NLRP3 inflammatory vesicles, IL-1β, and IL-18 levels were sequentially decreased in the chronic insomnia co-morbid OSAHS group, chronic insomnia group, and control group, respectively (P < 0.05). Pearson correlation analysis of patients in the chronic insomnia co-morbid OSAHS group showed that serum NLRP3 inflammatory vesicles, IL-1β, and IL-18 levels were positively correlated (P < 0.05) with PSQI score, total time to awaken after sleep, N1%, and AHI, and positively correlated with total sleep time, TS90%, visuospatial and executive ability, delayed recall ability, and total MoCA score negatively correlated (P < 0.05); IL-1β and IL-18 levels were negatively correlated with N3% (P < 0.05); and NLRP3 inflammatory vesicles and IL-18 levels were negatively correlated with attention (P < 0.05). Multiple linear regression analysis showed that serum NLRP3 inflammatory vesicles levels affected PSQI scores, N1%, N3%, AHI, TS90% and attention, IL-1β levels affected PSQI scores, N1%, N3%, TS90%, attention and delayed recall ability, and IL-18 levels affected AHI, TS90% and delayed recall ability (P < 0.05).Conclusions Serum NLRP3 inflammatory vesicles, IL-1β, and IL-18 levels were elevated in patients with chronic insomnia co-morbid OSAHS compared to patients with chronic insomnia and normal subjects, and elevated serum NLRP3 inflammatory vesicles, IL-1β, and IL-18 were associated with decreased sleep quality and impaired cognitive function.