阻塞性睡眠呼吸暂停患者外周血单个核细胞中NLRP3炎症小体相关指标表达及其临床相关性

Expression of NLRP3 inflammasome-related markers in peripheral blood mononuclear cells and their clinical correlations in patients with obstructive sleep apnea

摘要

目的 探讨阻塞性睡眠呼吸暂停（OSA）患者外周血单个核细胞（PBMC）中NLRP3炎症小体相关指标的表达特征及其与病情严重程度的关系。方法 采用横断面研究设计,连续纳入2024年1-12月在遵义医科大学附属医院行整夜多导睡眠监测（PSG）的受试者。采用ELISA检测PBMC中NLRP3、Caspase-1蛋白水平及血清IL-1β水平,分析其在不同严重程度OSA患者中的变化及其与睡眠呼吸暂停低通气指数（AHI）、最低血氧饱和度的关联。结果 与对照组相比,中、重度OSA组PBMC中NLRP3、Caspase-1蛋白水平及血清IL-1β水平均升高,且重度OSA组升高更明显（P＜0.05）。OSA患者中,NLRP3与Caspase-1、IL-1β均呈正相关（r值分别为0.672、0.846,P＜0.001）,Caspase-1与IL-1β亦呈正相关（r=0.773,P＜0.001）。相关性分析显示,AHI与NLRP3、Caspase-1及IL-1β均呈正相关（r值分别为0.839、0.880、0.853,P＜0.05）,LSaO₂与上述指标均呈负相关（r值分别为-0.657、-0.613、-0.585,P＜0.001）。多因素线性回归分析结果表明,校正年龄、体质量指数及血脂等因素后,NLRP3仍与AHI独立相关（β=1.025,P＜0.001）。结论 OSA患者PBMC中NLRP3炎症小体相关指标表达水平升高,且与病情严重程度和夜间低氧程度相关。NLRP3炎症小体相关通路可能参与OSA相关炎症反应,并有望成为反映疾病严重程度的潜在辅助生物学指标。

Abstract

Objective To investigate the expression characteristics of NLRP3 inflammasome-related markers in peripheral blood mononuclear cells (PBMCs) of patients with obstructive sleep apnea (OSA) and their association with disease severity. Methods A cross-sectional study was conducted. Subjects who underwent overnight polysomnography (PSG) at the Affiliated Hospital of Zunyi Medical University from January to December 2024 were consecutively enrolled. Enzyme-linked immunosorbent assay (ELISA) was used to detect the protein levels of NLRP3 and Caspase-1 in PBMCs, as well as serum IL-1β levels. Differences among OSA patients with varying severities and their correlations with apnea-hypopnea index (AHI) and lowest oxygen saturation (LSaO₂) were analyzed. Results Compared with the control group, the levels of NLRP3 and Caspase-1 proteins in PBMCs and serum IL-1β were significantly increased in patients with moderate and severe OSA, with more pronounced elevations observed in the severe OSA group (P<0.05). In OSA patients, NLRP3 was positively correlated with Caspase-1 and IL-1β (r=0.672 and 0.846, respectively, P<0.001), and Caspase-1 was also positively correlated with IL-1β (r=0.773, P<0.001). Correlation analysis showed that AHI was positively correlated with NLRP3, Caspase-1, and IL-1β (r=0.839, 0.880, and 0.853, respectively, P<0.05), while LSaO₂ was negatively correlated with these markers (r=-0.657, -0.613, and -0.585, respectively, P<0.001). Multivariate linear regression analysis indicated that, after adjusting for age, body mass index, and blood lipids, NLRP3 remained independently associated with AHI (β=1.025, P<0.001). Conclusion The expression of NLRP3 inflammasome-related markers in PBMCs is elevated in patients with OSA and is associated with disease severity and nocturnal hypoxia. The NLRP3 inflammasome pathway may be involved in OSA-related inflammatory responses and could serve as a potential biomarker reflecting disease severity.

关键词

阻塞性睡眠呼吸暂停 / NLRP3炎症小体 / 间歇性低氧 / 多导睡眠监测

Key words

obstructive sleep apnea / NLRP3 inflammasome / intermittent hypoxia / polysomnography

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基金资助

遵义市科技计划项目(遵市科合HZ字(2019)75)