The role of TLR4/NF-κB signaling pathway in sleep deprivation induced Meniere's disease
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摘要: 目的 通过检测梅尼埃病(Meniere's disease，MD)患者外周血中TLR4/NF-κB(Toll-like receptor-4/nuclear factor-κB，TLR4/NF-κB)信号通路相关蛋白及下游促炎细胞因子含量、收集匹兹堡睡眠质量指数量表(pittsburgh sleep quality index，PSQI)，探讨睡眠障碍与MD可能的相关性，以及TLR4/NF-κB信号通路在睡眠障碍诱发MD中的作用。方法 选取MD患者32例(MD组)，同期无中耳及内耳相关疾病的患者家属20例(对照组)，收集所有受试者基本资料、PSQI、晨起空腹外周血，使用酶联免疫吸附试验检测白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、单核细胞趋化因子-1(MCP-1)、Toll样受体4(TLR4)、核因子-κB(NF-κB)在外周血的水平，并对所得数据进行统计学分析。结果 ① MD组PSQI分值显著高于对照组，差异有统计学意义(P < 0.01)；MD组PSQI中的7个因子分值均高于对照组，其中因子2、4、6较对照组差异有统计学意义。②在MD组中睡眠障碍者共18例，患病率为56.25%，其中男性6例，患病率为50.00%(6/12)，女性12例，患病率为60.00%(12/20)。③MD组、MD的睡眠障碍组及MD的非睡眠障碍组5个测试指标水平均高于对照组，其中MD组TLR4、NF-κB水平显著高于对照组，差异均有统计学意义(P < 0.05)；睡眠障碍组IL-1β、TNF-α、TLR4、NF-κB水平显著高于对照组，差异均有统计学意义(P < 0.05)。MD的睡眠障碍组5个测试指标水平均高于MD组及MD患者的非睡眠障碍组，差异无统计学意义。MD组5个测试指标水平均高于MD患者的非睡眠障碍组，差异无统计学意义。结论 ① 睡眠障碍可能是部分MD的重要诱发因素之一，睡眠障碍对MD的影响存在性别差异。②存在睡眠障碍的MD患者外周血中TLR4/NF-κB信号通路相关蛋白及下游促炎细胞因子含量增加，睡眠障碍可能通过激活TLR4/NF-κB信号通路诱发MD。
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关键词:
- 梅尼埃病 /
- 睡眠障碍 /
- TLR4/NF-κB信号通路
Abstract: Objective By detecting the levels of proteins in the Toll-like receptor-4/nuclear factor-κB (TLR4/NF-κB) signaling pathway and downstream proinflammatory cytokines in peripheral blood of patients with Meniere's disease (MD), Pittsburgh Sleep Quality Index (PSQI) scores were collected to investigate the correlation between sleep disorders and MD and the role of TLR4/NF-κB signaling pathway in mediating sleep disorders inducing MD.Methods Thirty-two MD patients and 20 family members of patients without middle ear and inner ear related diseases were selected. Basic data, PSQI and fasting peripheral blood of all subjects were collected. Enzyme linked immunosorbent assay.The levels of interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), monocyte chemokine-1(MCP-1), Toll-like receptor 4(TLR4) and nuclear factor-κB(NF-κB) in peripheral blood were detected by ELISA, and the data were statistically analyzed.Results ① PSQI score of MD group was higher than that of normal control group, and the difference was statistically significant(P < 0.01); The scores of every factors of PSQI in MD group were higher than those in normal control group, and the scores of factors 2, 4 and 6 were significantly different from those in normal control group. ②In the MD group, there were 18 patients with sleep disorders, with a prevalence rate of 56.25%, including 6 males with a prevalence rate of 50.00% and 12 females with a prevalence rate of 60.00%. ③The levels of five test indexes in MD group, sleep disorder group and non-sleep disorder group were higher than those in control group, and the levels of TLR4 and NF-κB in MD group were significantly different from those in control group(P < 0.05). The levels of IL-1β, TNF-α, TLR4 and NF-κB in sleep disorder group were significantly different from those in control group(P < 0.05). The levels of five test indexes in non-sleep disorder group were not statistically significant compared with those in control group. The levels of five test indexes in the MD sleep disorder group were higher than those in the MD group and the non-sleep disorder group, with no statistical significance. The levels of five test indexes in MD group were higher than those in non-sleep disorder group, with no statistical significance(P>0.05).Conclusion ① Sleep disorders may be one of the important predisposing factors of some MD, and the effects of sleep disorders on MD are different between the sexes. ②Sleep disorders may activate TLR4/NF-κB signaling pathway to induce MD. The selection of TLR4/NF-κB signaling pathway related proteins and downstream pro-inflammatory factor inhibitors to intervene MD may provide a new idea for protecting the hearing balance function of MD.-
Key words:
- Meniere's disease /
- sleep disorders /
- TLR4/NF-κB signaling pathway
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表 1 MD组与对照组PSQI的7个因子分值对比
X±S，M(P25，P75) 评分 MD组 对照组 Z/F P 主观睡眠质量 1.59±0.84 1.30±0.73 0.457 0.502 睡眠潜伏时间 2.00(1.00，3.00) 1.00(0.00，1.75) -2.530 0.011 总睡眠时间 0.84±0.81 0.70±0.57 1.426 0.238 睡眠效率 1.00(0.00，2.00) 0.00(0.00，1.00) -2.633 0.008 睡眠紊乱 1.19±0.47 0.70±0.47 0.731 0.396 催眠用药 0.00(0.00，1.00) 0.00(0.00，0.00) -2.571 0.010 日间功能障碍 0.00(0.00，1.00) 0.00(0.00，0.75) -1.653 0.098 
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表 2 不同组IL-1β、TNF-α、MCP-1、TLR4、NF-κB含量比较
pg/mL，M(P25，P75) IL-1β TNF-α MCP-1 TLR4 NF-κB MD睡眠障碍组 17.48
(11.34，139.21)1)30.42
(21.63，60.08)1)127.30
(85.25，166.85)167.63
(142.62，191.54)1)37.66
(30.82，41.98)1)MD非睡眠障碍组 15.89
(11.28，24.00)25.72
(17.58，35.36)115.34
(80.72，146.98)157.41
(149.70，167.51)31.91
(28.97，39.13)MD组 15.89
(11.70，28.75)28.91
(19.39，41.53)120.04
(85.12，141.53)163.61
(147.50，175.66)1)34.23
(29.98，41.51)1)对照组 9.84
(6.84，16.34)20.95
(16.75，25.81)83.09
(79.19，149.49)134.83
(124.43，148.05)26.99
(21.81，33.91)H 10.514 9.299 2.873 15.592 11.996 P 0.015 0.026 0.412 0.001 0.007 与对照组比较，1)P＜0.05。
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