中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (12): 2750-2754.doi: 10.4103/1673-5374.339499

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

NLRP3炎症小体通路参与噪声性听力损伤的发生

  

  • 出版日期:2022-12-15 发布日期:2022-05-05
  • 基金资助:
    国家自然科学基金(81770992,81970897);国家重点研发计划(2020YFC205200);和深圳市卫生和计划生育系统研究项目(SZXJ2018079);深圳三明项目(SZSM20162076)

Involvement of NLRP3-inflammasome pathway in noise-induced hearing loss

Na Sai1, 2, 3, 4, #, Yuan-Yuan Yang5, #, Long Ma6, Da Liu1, 2 ,3, 4, Qing-Qing Jiang1, 2, 3, 4, Wei-Wei Guo1, 2, 3, 4, *, Wei-Ju Han1, 2, 3, 4, *   

  1. 1College of Otolaryngology Head and Neck Surgery, Chinese PLA General Hospital, Beijing, China; 2National Clinical Research Center for Otolaryngologic Diseases, Beijing, China; 3Key Laboratory of Hearing Science, Ministry of Education, Beijing, China; 4Beijing Key Laboratory of Hearing Impairment for Prevention and Treatment, Beijing, China; 5Department of Otolaryngology Head and Neck Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong Province, China; 6PLA Rocket Force Characteristic Medical Center Department of Stomatology, China
  • Online:2022-12-15 Published:2022-05-05
  • Contact: Wei-Wei Guo, MD, gwent001@163.com; Wei-Ju Han, MD, PhD, hanweiju@aliyun.com.
  • Supported by:
    This work was supported by the National Key Research and Development Program of China, No. 2020YFC2005200 (to WWG and WJH), the National Nature Science Foundation of China, Nos. 81770992 (to NS and WJH), 81970897 (to WWG), and Health and Family Planning System Research Project of Shenzhen Municipality, No. SZXJ2018079 (to YYY), Shenzhen Sanming Project, No. SZSM201612076 (to YYY).

摘要:

炎症小体是细胞质中的一种多蛋白寡聚体,是先天免疫系统的一部分,在噪声性听力损伤(NIHL)的病理过程中起着关键作用。然而,NIHL中NLR家族Pyrin domain Containing 3(NLRP3)炎症小体的激活机制还未得到明确证明。实验中,小型猪被暴露在120 dB(A)的白噪声中,应用听觉脑干反应(ABR)检测听力功能。采用免疫荧光染色、共聚焦激光扫描成像技术、Western blot和定量RT-PCR分析炎症小体相关蛋白的分布和表达。结果发现,在白噪声暴露后,NLRP3、白细胞介素1β(IL-1β)、白细胞介素18(IL-18)和裂解caspase-1在内耳中高表达。这些结果表明,NLRP3炎症小体在耳蜗中可能在噪声性听力损伤后被激活,炎症小体是潜在的防治噪声性耳聋的新靶点。

https://orcid.org/0000-0002-2001-7956 (Wei-Wei Guo); https://orcid.org/0000-0002-8739-481X (Wei-Ju Han)

Abstract: The inflammasome is a multiprotein oligomer in the cell cytoplasm and is part of the innate immune system. It plays a crucial role in the pathological process of noise-induced hearing loss (NIHL). However, the mechanisms of NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in NIHL have not been clearly demonstrated. In this study, miniature pigs were exposed to white noise at 120 dB(A) and auditory brainstem response measurements were used to measure their hearing function. Immunofluorescence staining, confocal laser scanning microscopy, western blot assay, and quantitative reverse transcription-polymerase chain reaction were used to analyze inflammasome-related protein distribution and expression. NLRP3, interleukin-1β, interleukin-18, and cleaved-caspase-1 were highly expressed in the cochlea after 120 dB(A) white noise exposure. Our findings suggest that NLRP3-inflammasomes in the cochlea may be activated after acoustic trauma, which may be an important mechanism of noise-induced hearing loss.

Key words: acoustic injury, inflammasome, interleukin-1β, miniature pig, NLR family pyrin domain containing 3 (NLRP3), noise-induced hearing loss, sensorineural hearing loss