噪声损伤引起小鼠耳蜗炎症复合体NLRP3激活及氢气的抑制作用  

Noise-induced NLRP3 Activation and Inhibiting by Hydrogen in Mice Cochlei

作　　者：刘达 塞娜[1] 秦含黛 王建泽 孙健斌 张桐[1] 郭维维[1] 于宁[1] 韩维举[1] LIU Da;SAI Na;QIN Handai;WANG Jianze;SUN Jianbin;ZHANG Tong;GUO Weiwei;YU Ning;HAN Weiju(Department of Otorhinolaryngology Head and Neck Surgery,Chinese PLA General Hospital,Chinese PLA Medical School,National Clinical Research Center for Otorhinolaryngology Diseases,Beijing 100853 China)

机构地区：[1]解放军总医院耳鼻咽喉头颈外科医学部,国家耳鼻咽喉疾病临床医学研究中心,北京100853

出　　处：《中华耳科学杂志》2022年第1期116-120,共5页Chinese Journal of Otology

基　　金：国家自然科学基金面上项目(81770992);国家重点研发项目(2020YFC2004001)。

摘　　要：目的探讨噪声损伤引起小鼠耳蜗炎症复合体NLRP3及半胱氨酸蛋白酶-1的激活,以及氢气吸入的抑制作用。方法选取30只8周龄C57小鼠随机分为对照组、噪声组和噪声+氢气组。免疫荧光和蛋白质免疫印迹法比较各组小鼠耳蜗NLRP3及半胱氨酸蛋白酶-1的分布和含量变化。ELISA法检测各组耳蜗淋巴液IL-1β、IL-6和IL-10浓度。检测各组听性脑干反应阈值以评估听功能。应用SPSS21.0软件进行统计学分析。结果NLRP3、半胱氨酸蛋白酶-1在内耳毛细胞中表达,噪声后二者表达均显著增加(P<0.05),氢气干预7天后相比噪声组显著降低(P<0.05)。与对照组相比,噪声组耳蜗淋巴液IL-1β(P<0.05)、IL-6升高(P<0.01),IL-10降低(P<0.05)。氢气干预后与噪声组相比IL-1β显著降低(P<0.05)、IL-6显著降低(P<0.01),IL-10显著增加(P<0.01)。噪声暴露后小鼠听性脑干反应阈值较对照组显著升高(P<0.05);噪声组和噪声+氢气组听性脑干反应阈值在噪声暴露后1天无显著差异(P>0.05),在7天后氢气组阈值较低,在24kHz具有显著差异(P<0.05)。结论噪声损伤后小鼠耳蜗炎症复合体NLRP3表达增加,引起caspase-1激活及下游炎症因子IL-1β、IL-6释放,是噪声性听力损失的重要原因之一。吸入氢气可能通过抑制炎症复合体的表达,减轻噪声损伤引起的耳蜗炎症反应,促进听力恢复。Objective To study the activation of NLRP3 and caspase-1 in mice cochlea after noise exposure and whether hydrogen inhalation can inhibit NLRP3 expression.Method Thirty 8-week-old C57 mice were randomly divided into a normal control group,a noise exposure group and hydrogen treatment group with equal numbers.Immunofluorescence staining was used to demonstrate the distribution of NLRP3 and caspase-1.Expression of NLRP3 and caspase-1 proteins in the cochlea was detected by Western Blot.Concentration of IL-1β,IL-6 and IL-10 in cochlear lymphatic fluid was assessed by ELISA.Auditory brainstem response(ABR)thresholds were recorded.The SPSS 21.0 software was used for statistical analysis.Results NLRP3 and caspase-1 were expressed in hair cells and significantly increased with noise exposure(P<0.05),but lower after 7 days of hydrogen intervention compared with the noise exposure only group(P<0.05).Compared with the control,levels of IL-1β(P<0.05),IL-6(P<0.01)and IL-10(P<0.05)increased in the cochlea fluid with noise exposure.With hydrogen intervention,Il-1β(P<0.05)and IL-6 were decreased(P<0.01),with increased IL-10(P<0.01)compared with the noise exposure only group.ABR thresholds were elevated after noise exposure(P<0.05),even with hydrogen treatment at 1 day(P>0.05),although threshold at 24 kHz improved at 7 days after hydrogen inhalation compared to the noise exposure only group(P<0.05).Conclusion NLRP3 expression of the cochlea is increased after noise injury,leading to the activation of caspase-1 and the release of inflammatory factors IL-1βand IL-6,which are an important cause of noise-induced hearing loss.Hydrogen inhalation may reduce cochlear inflammation and promote hearing recovery by inhibiting the expression of NLRP3.

关 键 词：噪声性耳聋 炎症复合体 氢气 

分 类 号：R764[医药卫生—耳鼻咽喉科]