BMAL1-睡眠相互作用调节昼夜节律失调的过敏性鼻炎患者的生活质量

文献信息

中文摘要

背景： 昼夜节律CLOCK基因调控睡眠和昼夜节律。过敏性鼻炎（AR）常与睡眠障碍相关，睡眠障碍可显著损害患者的生活质量（QoL）。然而，AR中昼夜节律CLOCK基因表达与睡眠相关结局或QoL之间的关系尚未确立。方法：本研究纳入133名参与者（100例AR患者和33名健康对照）。参与者完成了晨型-夜型问卷（MEQ）、鼻结膜炎生活质量问卷（RQLQ）和匹兹堡睡眠质量指数（PSQI）。采用qRT-PCR检测外周血白细胞中昼夜节律CLOCK基因表达。使用Mann-Whitney U检验比较两个独立组，分类变量采用卡方检验分析。线性回归评估昼夜节律CLOCK基因表达与RQLQ或睡眠参数之间的关联。结果：与对照组相比，AR患者表现出显著更差的睡眠质量、更长的入睡潜伏期、更频繁的夜间觉醒、更高的夜型chronotype患病率以及外周白细胞中昼夜节律基因表达失调。具体而言，CLOCK和PER1上调，BMAL1和CRY1下调。在AR患者中，CLOCK表达与PSQI评分呈正相关，与睡眠时长呈负相关，而PER2、CRY1和CRY2与睡眠时长呈正相关。BMAL1表达与RQLQ总分、活动受限和鼻部症状呈正相关。此外，BMAL1在活动受限方面与睡眠时长存在显著交互作用，在鼻部症状方面与睡眠效率存在显著交互作用。结论：AR患者表现出昼夜节律失调，包括CLOCK基因失衡、睡眠差和夜型chronotype。BMAL1-睡眠相互作用显著影响生活质量。在临床上，通过睡眠卫生或时间疗法等干预措施靶向该轴，可在常规护理获益之外改善鼻部症状和日常功能。

英文摘要

Circadian CLOCK genes regulate sleep and circadian rhythms. Allergic rhinitis (AR) is frequently associated with sleep disturbances that can substantially impair patient quality of life (QoL). However, the relationship between circadian CLOCK gene expression in AR and sleep-related outcomes or QoL has not been established. This study included 133 participants (100 patients with AR and 33 healthy controls). Participants completed the Morningness-Eveningness Questionnaire (MEQ), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), and Pittsburgh Sleep Quality Index (PSQI). Circadian CLOCK gene expression in peripheral blood leukocytes was measured using qRT-PCR. The Mann-Whitney U test was used to compare the two independent groups and categorical variables were analyzed using the chi-square test. Linear regression evaluated the associations between circadian CLOCK gene expression and the RQLQ or sleep parameters. Patients with AR demonstrated significantly poorer sleep quality, longer sleep latency, more frequent nocturnal awakenings, and a higher prevalence of evening-type chronotypes along with dysregulated circadian gene expression in peripheral leukocytes compared to controls. Specifically, CLOCK and PER1 were upregulated and BMAL1 and CRY1 were downregulated. CLOCK expression was positively correlated with PSQI scores and negatively correlated with sleep duration in patients with AR, whereas PER2, CRY1, and CRY2 were positively correlated with sleep duration. BMAL1 expression was positively correlated with the total RQLQ score, activity limitations, and nasal symptoms. Furthermore, BMAL1 exhibited significant interactions with sleep duration on activity limitations and with sleep efficiency on nasal symptoms. Patients with AR exhibit circadian dysregulation, including imbalanced CLOCK genes, poor sleep, and evening chronotypes. The BMAL1-sleep interaction significantly influences the quality of life. Clinically, targeting this axis through interventions, such as sleep hygiene or chronotherapy, can enhance nasal symptoms and daily functioning beyond the benefits of conventional care.