Department of Clinical Biochemistry, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Department of Clinical Biochemistry, School of Medicine, Shahid Behehshti University of Medical Sciences, Tehran, Iran.
Eur J Neurol. 2022 Dec;29(12):3647-3657. doi: 10.1111/ene.15540. Epub 2022 Sep 12.
There is some evidence that cytokines may play an important role in sleep deprivation; however, the underlying mechanisms are still unknown. So, the present study aimed to evaluate the relationship between NOD-like receptor protein 1 (NLRP1) and NOD-like receptor protein 3 (NLRP3) inflammasome activation of blood cells and serum levels of cytokines in individuals with chronic insomnia disorder (CID).
Blood samples were collected from 24 individuals with CID and 24 healthy volunteers. The inflammasome activation was evaluated using real-time polymerase chain reaction of NLRP1, NLRP3, apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) and caspase-1; western blot of NLRP1 and NLRP3; caspase-1 activity assay; and serum levels of interleukin-1β (IL-1β), IL-18 and other cytokines using enzyme-linked immunosorbent assay. Reactive oxygen species generation in blood cells were detected by flow cytometry assay. Also, magnetic resonance imaging scans were obtained on a Siemens Magnetom Avanto 1.5 T MRI whole-body scanner using an eight-channel head coil.
Increased activity of NLRP1 and NLRP3 inflammasomes in blood cells, increased serum levels of pro-inflammatory cytokines and decreased serum levels of IL-10 and transforming growth factor β in individuals with CID were found. Significant correlation was observed between increased serum concentration of IL-1β and the severity of insomnia in individuals with CID. The levels of reactive oxygen species in blood cells were found to be correlated with IL-1α and tumor necrosis factor α concentrations in sera from individuals with CID. Moreover, the individuals with CID demonstrated increased right cerebellum cortex and lateral ventricle mean diffusivity bilaterally compared to controls.
This study provided new insights on the pathogenesis of CID and the effects of cytokines on inflammasome activation.
有证据表明细胞因子可能在睡眠剥夺中发挥重要作用，但潜在机制尚不清楚。因此，本研究旨在评估慢性失眠障碍（CID）患者血细胞中 NOD 样受体蛋白 1（NLRP1）和 NOD 样受体蛋白 3（NLRP3）炎性小体激活与血清细胞因子水平之间的关系。
采集 24 例 CID 患者和 24 例健康志愿者的血样。通过 NLRP1、NLRP3、凋亡相关斑点样蛋白含有半胱氨酸蛋白酶募集域（ASC）和半胱天冬酶-1 的实时聚合酶链反应、NLRP1 和 NLRP3 的 Western blot、半胱天冬酶-1 活性测定、酶联免疫吸附试验测定白细胞介素-1β（IL-1β）、IL-18 和其他细胞因子的血清水平，检测血细胞中活性氧的生成。使用西门子 Magnetom Avanto 1.5 T MRI 全身扫描仪和 8 通道头部线圈进行磁共振成像扫描。
CID 患者血细胞中 NLRP1 和 NLRP3 炎性小体活性增加，促炎细胞因子血清水平升高，IL-10 和转化生长因子β血清水平降低。CID 患者血清中 IL-1β 浓度增加与失眠严重程度呈显著相关。还发现，CID 患者的血细胞中活性氧水平与血清中 IL-1α 和肿瘤坏死因子α的浓度相关。此外，CID 患者与对照组相比，双侧小脑皮质和侧脑室平均扩散率增加。
本研究为 CID 的发病机制和细胞因子对炎性小体激活的影响提供了新的见解。
