睡眠剥夺与噪声联合暴露对海马神经炎症及细胞焦亡的影响

摘要/Abstract

摘要： 目的了解睡眠剥夺与噪声联合暴露对海马神经炎症及细胞焦亡的影响,为明确二者对神经系统协同效应及机制提供线索。方法 48只雄性C57BL/6J小鼠随机分为对照组（control,C）、单纯睡眠剥夺组（sleep deprivation,SD）、单纯噪声暴露组（noise exposure,NE）及睡眠剥夺与噪声联合暴露组（sleep deprivation+noise exposure,SN）4组,采用小鼠置于水中以防止其蜷缩睡眠（curling prevention by water,CPW）模式建立睡眠剥夺小鼠模型,噪声强度为115 dB SPL,持续时间为4 h。采用试剂盒检测小鼠海马组织中超氧化物歧化酶（superoxide dismutase,SOD）活性水平及丙二醛（malonaldehyde,MDA）含量水平,酶联免疫吸附（enzyme-linked immunosorbent assay,ELISA）法检测小鼠血清中皮质酮（corticosterone,CORT）水平,实时荧光定量PCR（quantitative real-time PCR,RT-qPCR）法和蛋白质印迹（Western Blot）法检测小鼠海马组织中炎症因子及细胞焦亡相关基因和蛋白的表达。结果睡眠剥夺及噪声暴露后,与C组相比,SD组小鼠血清中CORT含量显著上升（P<0.05）,NE组血清CORT含量有上升趋势但差异无统计学意义（P>0.05）,SN组血清CORT含量显著上升（P<0.05）;睡眠剥夺及噪声暴露可引起海马组织氧化还原平衡的紊乱,与C组相比,SD组、NE组及SN组海马组织中SOD活性显著下降（P<0.05）,且MDA含量显著上升（P<0.05）;SD组、NE组及SN组海马组织中肿瘤坏死因子-α（tumor necrosis factor-α,TNF-α）、白介素-6（interleukin-6,IL-6）、白介素-18（Interleukin-18,IL-18）及白介素-1β（interleukin-1β,IL-1β）mRNA表达水平较C组均显著上升（P<0.05）。进一步分析显示,与C组相比,SD组、NE组及SN组海马焦亡相关核苷酸结合寡聚化结构域样受体蛋白3（NOD-like receptor thermal protein domian associated protein 3,NLRP3）/半胱天冬酶-1（cysteine aspartate-specific protease1,Caspase-1）/消皮素 D（gasdermin-D,GSDMD）通路影响显著（P<0.05）,且析因分析结果显示睡眠剥夺和噪声联合暴露对焦亡相关蛋白的表达有交互作用（P<0.05）。结论睡眠剥夺和噪声单独及联合暴露均引起海马发生神经炎症反应,导致神经细胞焦亡,且二者存在协同效应,最终可能增加神经系统损伤的风险。

关键词: 睡眠剥夺, 噪声, NLRP3/Caspase-1/GSDMD通路, 细胞焦亡

Abstract: Objective To explore the effects of sleep deprivation and noise combined exposure on hippocampal neuroinflammation and pyroptosis,and to provide clues for clarifying the synergistic effects and mechanisms of these factors on the nervous system. Methods Forty-eight male C57BL/6J mice were randomly divided into four groups：the control(C) group,the sleep deprivation(SD) group,the noise exposure(NE) group,and the sleep deprivation combined with noise exposure(SN) group. The sleep deprivation paradigm was established by employing the curling prevention by water(CPW) paradigm. The noise intensity was 115 dB SPL,and the duration lasted for 4 hours. The activity level of superoxide dismutase(SOD) and the content level of malonaldehyde(MDA) in the hippocampal tissues of the mice were determined using kits. The level of corticosterone(CORT) in the serum of the mice was detected by enzyme-linked immunosorbent assay(ELISA). The expressions of inflammatory factors and genes and proteins related to pyroptosis in the hippocampal tissues of the mice were measured by quantitative real-time PCR(RT-qPCR) and Western Blot. Results Following sleep deprivation and noise exposure,the serum CORT levels in SD group of mice were significantly increased in comparison to C group(P<0.05). The serum CORT levels in NE group demonstrated an upward trend,yet the difference was not statistically significant(P>0.05). The serum CORT levels in SN group were significantly increased(P<0.05). Compared with C group,the SOD activity in the hippocampus tissue of SD,NE and SN groups were significantly decreased(all P<0.05),and the MDA content were significantly increased(all P<0.05). These findings suggested that sleep deprivation and noise exposure could induce disturbances in the oxidation-reduction balance of hippocampal tissues. Additionally,the expression levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-18(IL-18) and interleukin-1β(IL-1β) mRNA in the hippocampal tissues of SD,NE and SN groups were observed to have increased significantly in comparison to that of C group(all P<0.05). Further analysis revealed that compared to C group,SD,NE and SN groups exerted a pronounced influence on the hippocampal NOD-like receptor thermal protein domian associated protein 3(NLRP3)/cysteine aspartate-specific protease1(Caspase-1)/gasdermin-D(GSDMD) pathway associated with pyroptosis(all P<0.05). Additionally,factorial analysis indicated that sleep deprivation and combined noise exposure exerted an interactive effect on the expression of pyroptosis-related proteins(P<0.05). Conclusion Sleep deprivation and noise exposure alone and in combination can cause neuroinflammatory responses in the hippocampus,leading to neuronal pyroptosis,and the two have a synergistic effect,ultimately increasing the risk of neurological damage.

Key words: Sleep deprivation, Noise, NLRP3/Caspase-1/GSDMD pathway, Pyroptosis

中图分类号:

R-332

宋晓琼, 程梦竹, 马科锋, 佘晓俊, 崔博. 睡眠剥夺与噪声联合暴露对海马神经炎症及细胞焦亡的影响. [J]职业与健康, 2025, 41(22): 3074-3080.

SONG Xiaoqiong, CHENG Mengzhu, MA Kefeng, SHE Xiaojun, CUI Bo. Effects of combined sleep deprivation and noise exposure on hippocampal neuroinflammation and pyroptosis. [J]OCCUPATION AND HEALTH, 2025, 41(22): 3074-3080.

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