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突发性感音神经性耳聋（sudden sensorineural hearing loss,SSNHL）又称突发性耳聋，是指72 h内发生的原因不明的感音神经性耳聋，至少相邻两个频率听力下降≥20 dB HL，该病的年发病率近年来有上升趋势，主要影响中年人群。目前，临床上治疗SSNHL的首选治疗方案为全身应用皮质类固醇治疗，但是在实际治疗过程中，约30%～50%患者反应不佳，且部分患者使用皮质类固醇药物有很大的不良反应，因此探索新的治疗手段尤为重要。全身免疫紊乱通过循环炎症因子、自身抗体及免疫细胞浸润等途径影响内耳局部微环境，破坏其免疫豁免状态，最终导致常以单侧为表现的听力损失。自身抗体沉积、T细胞亚群失调及巨噬细胞过度活化等异常免疫反应，进一步加重内耳组织损伤。同时，外周血中的中性粒细胞与淋巴细胞比值、血小板与淋巴细胞比值等及内耳局部的HSP70、prestin等生物标志物与病情相关。临床上，目前基于免疫炎症机制的靶向治疗已经取得较好的进展，如靶向NLRP3通路、JNK信号通路及抗氧化应激等。此外，还有针对细胞保护、功能修复的小分子药物及基因治疗等新兴研究为SSNHL的治疗提供保障。但是，当前研究仍面临多重挑战，例如现有治疗方案疗效有限、生物标志物谱系异质性显著、血-迷路屏障导致的药物递送障碍，以及病因学的高度异质性等问题。未来研究需在发病机制深度解析、精准生物标志物筛选、高效药物递送系统开发等关键领域实现突破，从而推动SSNHL临床诊疗水平的系统性提升。
Abstract：Sudden sensorineural hearing loss(SSNHL) refers to idiopathic sensorineural hearing loss occurring within 72 hours, characterized by a hearing loss of at least 30 dB at two adjacent frequencies. The annual incidence of this condition has shown an increasing trend in recent years, primarily affecting the middle-aged population. Currently, systemic corticosteroid therapy is the first-line treatment for SSNHL. However, approximately 30% to 50% of patients exhibit poor response to treatment, and some experience significant side effects from corticosteroid use, making developing new therapeutic approaches crucial. Systemic immune dysregulation affects the local microenvironment in the inner ear through inflammatory factors, autoantibodies and immune cell infiltration, disrupting its immune-privileged state and ultimately leading to unilateral hearing loss. Abnormal immune responses, such as autoantibody deposition, T-cell subset dysregulation, and macrophage hyperactivation, further exacerbate inner ear tissue damage. Additionally, biomarkers such as NLR and PLR in peripheral blood, as well as HSP70 and prestin in the inner ear, are associated with disease progression. Clinically, targeted therapies based on immunoinflammatory mechanisms have achieved notable progress, including those targeting the NLRP3 pathway, JNK signaling pathway and antioxidant stress. Furthermore, emerging research on cell-protective and functional-repairing small-molecule drugs and gene therapy provides a foundation for treating sudden deafness. However, current research still faces multiple challenges, such as limited efficacy of existing treatments, significant heterogeneity in biomarker profiles, drug delivery barriers due to the blood-labyrinth barrier, and high heterogeneity in etiology. Future research needs to achieve breakthroughs in key areas such as in-depth elucidation of pathogenesis, precise biomarker screening and development of efficient drug delivery systems, thereby promoting a systematic improvement in the clinical diagnosis and treatment of SSNHL.
[1]Lee HA,Chung JH.Contemporary review of idiopathic sudden sensorineural hearing loss:management and prognosis[J].J Audiol Otol,2024,28(1):10-17.DOI:10.7874/j ao.2024.00024.
[2]Ko HY,Nam H J,Kim MH.A nationwide population-based study for the recurrence and comorbidities in sudden sensorineural hearing loss[J].Laryngoscope,2024,134(3):1417-1425.DOI:10.1002/lary.31024.
[3]Conlin AE,Parnes LS.Treatment of sudden sensorineural hearing loss:Ⅱ.a meta-analysis[J].Arch Otolaryngol Head Neck Surg,2007,133(6):582-586.DOI:10.1001/archotol.133.6.5 82.
[4]刘静,王大勇,马静,等.突发性聋患者自我管理研究进展[J].中华耳科学杂志,2025,23(3):505-508.DOI:10.3969/j.issn.1672-2922.2025.03.027.
[5]Yamada S,Kita J,Shinmura D,et al.Update on findings about sudden sensorineural hearing loss and insight into its pathogenesis[J].J Clin Med,2022,11(21):63 87.DOI:10.3390/jcm112163 87.
[6]Mingbao Y,Bei Z,Yafeng G,et al.Perfusion steroid via ventilation tube as salvage treatments for sudden sensorineural hearing loss[J].Ear Nose Throat J,2024,24:1455613241284154.DOI:10.1177/01455613241284154.
[7]Chrysouli K,Kollia P,Papanikolaou V,et al.The effectiveness of intratympanic steroid injection in addition to systemic corticosteroids in the treatment of idiopathic sudden sensorineural hearing loss[J].Am J Otolaryngol,2023,44(4):103872.DOI:10.1016/j.amjoto.2023.103872.
[8]Plontke SK,Girndt M,Meisner C,et al.Efficacy and safety of systemic,high-dose glucocorticoid therapy for idiopathic sudden sensorineural hearing loss:study protocol for a three-armed,randomized,triple-blind,multicenter trial(HODOKORT)[J].HNO,2022,70(Suppl2):30-44.DOI:10.1007/s00106-022-01184-8.
[9]中华耳鼻咽喉头颈外科杂志编辑委员会,中华医学会耳鼻咽喉头颈外科学分会.突发性聋诊断和治疗指南(2015)[J].中华耳鼻咽喉头颈外科杂志,2015,50(6):443-447.DOI:10.3760/cma.j.issn.1673-0860.2015.06.002.
[10]Arunthanachaikul T,Osothsinlp S,Nivatwongs S,et al.Prevalence and intriguing clinical profiles of autoimmune inner ear diseases in sudden sensorineural hearing loss[J].Otol Neurotol,2025,46(2):215-220.DOI:10.1097/MAO.0000000000004391.
[11]Cohen BE,Durstenfeld A,Roehm PC.Viral causes of hearing loss:a review for hearing health professionals[J].Trends hear,2014,18:2331216514541361.DOI:10.1177/2331216514541361.
[12]Sung CYW,Seleme MC,Payne S,et al.Virus-induced cochlear inflammation in newborn mice alters auditory function[J].JCI insight,2019,4(17):e128878.DOI:10.1172/j ci.insight.128878.
[13]Qiao XF,Li X,Wang GP,et al.Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in patients with sudden sensorineural hearing loss[J].Med princ pract,2019,28(1):23-27.DOI:10.115 9/000494556.
[14]Abdelhak BH,Elbadry MM,Abdelhak LH.Sudden sensorineural hearing loss(SSNHL):diagnostic and prognostic value of laboratory testing[J].Saudi J Otorhinolaryngol Head Neck Surg,2011,13(1):5-10.DOI:10.4103/1319-8491.274743.
[15]Li P,Qian T,Sun S.Spatial architecture of the cochlear immune microenvironment in noise-induced and age-related sensorineural hearing loss[J].Int Immunopharmacol,2023,114:109488.DOI:10.1016/j.intimp.2022.109488.
[16]Ralli M,D'Aguanno V,Di Stadio A,et al.Audiovestibular symptoms in systemic autoimmune diseases[J].J Immunol Res,2018,2018:5798103.DOI:10.1155/2018/5798103.
[17]Hajas A,Szodoray P,Barath S,et al.Sensorineural hearing loss in patients with mixed connective tissue disease:immunological markers and cytokine levels[J].J Rheumatol,2009,36(9):1930-1936.DOI:10.3899/jrheum.081314.
[18]Li L,Chen D,Lin X,et al.Understanding the role of inflammation in sensorineural hearing loss:current goals and future prospects[J].Brain-X,2023,1(3):e34.DOI:10.1002/brx2.34.
[19]Zhang Y,Li Y,Fu X,,et al.The detrimental and beneficial functions of macrophages after cochlear injury[J].Front Cell Dev Biol,2021,9:631904.DOI:10.3 3 89/fcell.2021.631904.
[20]Noonan KY,Lopez IA,Ishiyama G,et al.Immune response of macrophage population to cochlear implantation:cochlear immune cells[J].Otol Neurotol,2020,41(9):1288-1295.DOI:10.1097/MAO.0000000000002764
[21]Warchol ME.Interactions between macrophages and the sensory cells of the inner ear[J].Cold Spring Harb Perspect Med,2019,9(6):a033555.DOI:10.1101/cshperspect.a03 3 55 5.
[22]Dobbie AM.Evaluation and management of cytomegalovirus-associated congenital hearing loss[J].Curr Opin Otolaryngol Head Neck Surg,2017,25(5):390-395.DOI:10.1097/MOO.0000000000000401.
[23]Van de Steene V,Kuhweide R,Vlaminck S,et al.Varicella zoster virus:beyond facial paraly sis[J].Acta Otorhinolaryngol Belg,2004,58(1):61-66.
[24]Fanoy EB,Wolters BA,Topsakal V,et al.Three cases of hearing loss related to mumps during a nationwide outbreak in the netherlands,2009-2013[J].Pediatr Infect Dis J,2014,33(8):889-890.DOI:10.1097/INF.0000000000000320.
[25]Rappaport JM,Bhatt SM,Kimura RS,et al.Electron microscopic temporal bone histopathology in experimental pneumococcal meningitis[J].Ann Otol Rhinol Laryngol,1999,108(6):537-547.DOI:10.1177/000348949910800603.
[26]Wang W,Zhang LS,Zinsmaier AK,et al.Neuroinflammation mediates noise-induced synaptic imbalance and tinnitus in rodent models[J].PLoS Biol,2019,17(6):e3000307.DOI:10.1371/journal.pbio.3000307.
[27]Kang BC,Yi J,Kim SH,et al.Dexamethasone treatment of murine auditory hair cells and cochlear explants attenuates tumor necrosis factor-α-initiated apoptotic damage[J].PLOS One,2023,18(9):e0291780.DOI:10.1371/journal.pone.0291780.
[28]Kim HJ,Oh GS,Lee JH,et al.Cisplatin ototoxicity involves cytokines and STAT6 signaling network[J].Cell Res,2011,21(6):944-956.DOI:10.1038/cr.2011.27.
[29]Dinarello CA.Immunological and inflammatory functions of the interleukin-1 family[J].Annu Rev Immunol,2009,27:519-5 50.DOI:10.1146/annurev.immunol.021908.132612.
[30]LaPointe MC,Isenovic E.Interleukin-1beta regulation of inducible nitric oxide synthase and cyclooxygenase-2 involves the p42/44 and p3 8 MAPK signaling pathways in cardiac myocytes[J].Hypertension,1999,33(1 Pt 2):276-282.DOI:10.1161/01.hyp.33.1.276.
[31]Pathak S,Vambutas A.Autoimmune inner ear disease patient-associated 28-kDa pro inflammatory IL-1 β fragment results from caspase-7-mediated cle avage in vitro[J].JCI insight,2020,5(3):e130845.DOI:10.1172/jci.insight.130845.
[32]Vambutas A,Lesser M,Mullooly V,et al.Early efficacy trial of anakinra in cortico steroid-resistant autoimmune inner ear disease[J].J Clin Investc2014,124(9):4115-4122.DOI:10.1172/JCI76503.
[33]Ridker PM,Rane M.IL-6 in inflammation,immunity,and disease[J].Cold Spring Harb Perspect Biol,2014,6(10):a016295.DOI:10.1101/cshperspect.a016295.
[34]Vambutas A,Davia DV.Biologics for immune-mediated sensorineural hearing loss[J].Otolary ngol Clin North Am,2021,54(4):803-813.DOI:10.1016/j.otc.2021.05.005.
[35]Baeuerle PA,Henkel T.Function and activation of NF-kappa B in the immune system[J].Annu Rev Immunol,1994.12:141-179.DOI:10.1146/annurev.iy.12.040194.001041.
[36]Tong J,Hu C,Wu Y,et al.Radiation-induced NF-kB activation is involved in cochlear damage in mice via promotion of a local inflammatory response[J].J Radiat Res,2023,64(1):63-72.DOI:10.1093/jrr/rrac068.
[37]Garcia-MatoÁ,Cervantes B,Rodríguez-de la Rosa L,et al.IGF-1controls metabolic homeostasis and survival in HEI-OC1 auditory cells through AKT and mTOR signaling[J].Antioxidants(Basel Switz),2023,12(2):233.DOI:10.3390/antiox1202023 3.
[38]Guthrie GJ,Charles KA,Roxburgh CS,et al.The systemic inflammation-based neutrophil-lymphocyte ratio:experience in patients with cancer[J].Crit Rev Oncol Hematol,2013,88(1):218-230.DOI:10.1016/j.critrevonc.2013.03.010.
[39]Seo YJ,Jeong JH,Choi JY,et al.Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio:novel markers for diagnosis and progno sis in patients with idiopathic sudden sensorineural hearing loss[J].Dis Markers,2014,2014:702807.DOI:10.115 5/2014/702807.
[40]Kang JW,Kim MG,Kim SS,et al.Neutrophil-lymphocyte ratio as a valuable prognostic marker in idiopathic sudden sensorineural hearing loss[J].Acta Otolaryngol,2020,140(4):307-313.DOI:10.1080/00016489.2019.1705998.
[41]Foster CA,Breeze RE.The meniere attack:an ischemia/reperfusion disorder of inner ear sensory tissues[J].Med Hypotheses,2013,81(6):1108-1115.DOI:10.1016/j.mehy.2013.10.015.
[42]Frosolini A,Franz L,Daloiso A,et al.Digging into the role of inflammatory biomarkers in sudden sensorineural hearing loss diagnosis and prognosis:a systematic review and meta-analysis[J].Medicina(Kaunas),2022,58(7):963.DOI:10.3 390/medicina5 8070963.
[43]Bhattarai A,Tharu S,Sunar P,et al.Association of fibrinogen levels with sudden sensorineural hearing loss incidence and prognosis:a meta-analysis[M].Research Square,2023.DOI:10.21203/rs.3.rs-2541141/v1.
[44]Tukaj S.Heat shock protein 70 as a double agent acting inside and outside the cell:insights into auto immunity[J].Int J Mol Sci,2020,21(15):5298.DOI:10.3 3 90/ij ms21155298.
[45]Bloch DB,San Martin JE,Rauch SD,et al.Serum antibodies to heat shock protein 70 in sensorineural hearing loss[J].Arch Otolaryngol Head Neck Surg,1995,121(10):1167-1171.DOI:10.1001/archotol.1995.01890100075013.
[46]Harrison MS,Driscoll BG,Farnsworth J,et al.Characterization of ototoxic-induced prestin burst in the blood and implications for developing prestin as an ototoxicity biomarker[J].Research Square,2022.DOI:10.2120 3/rs.3.rs-2038495/v1.
[47]Stachler RJ,Chandrasekhar SS,Arc her SM,et al.Clinical practice guideline:sudden hearing loss[J].Otolaryngol Head Neck Surg,2012,146(3Suppl):S1-3 5.DOI:10.1177/01945 99812436449.
[48]Ehrchen JM,Roth J,Barczyk-Kahlert K.More than suppression:glucocorticoid action on monocytes and macrophages[J].Front Immunol,2019,10:2028.DOI:10.3 389/fimmu.2019.02028.
[49]Wang H,Zhao Z,Chen S.Local vs systemic use of steroids for sudden deafness with diabetes:a systematic review and meta-analysis[J].Ear Nose Throat J,2025,104(11):NP786-NP806.DOI:10.1177/01455613231170090.
[50]Tavares LCP,Caetano L de VN,Ianhez M.Side effects of chronic systemic glucocorticoid therapy:what dermatologists should know[J].An Bras Dermatol,2024,99(2):259-268.DOI:10.1016/j.abd.2023.05.005.
[51]Memar MY,Yekani M,Alizadeh N,et al.Hyperbaric oxygen therapy:antimicrobial mechanisms and clinical application for infections[J].Biomed Pharmacother,2019,109:440-447.DOI:10.1016/j.biopha.2018.10.142.
[52]Sen S,Sen S.Therapeutic effects of hyperbaric oxygen:integrated review[J].Med Gas Res,2021,11(1):30-33.DOI:10.4103/2045-9912.310057.
[53]苏林,马鑫,余力生.美国突发性聋临床实践指南(2019)高压氧治疗解析[J].中华耳鼻咽喉头颈外科杂志,2021,56(5):536-543.DOI:10.3760/cma.j.cn115 3 30-20200830-00709.
[54]Okano T.Immune system of the inner ear as a novel therapeutic target for sensorineural hearing loss[J].Front Pharmacol,2014,5:205.DOI:10.33 89/fphar.2014.00205.
[55]Gregory GE,Munro KJ,Couper KN,et al.The NLRP3 inflammasome as a target for sensorineural hearing loss[J].Clin Immunol(Orlando Fla,2023,249:109287.DOI:10.1016/j.clim.2023.109287.
[56]Wu Q,Xu M,Yao Y,et al.Targeting NLRP3/caspase-1/GSDMD to treat inner ear injury from labyrinthine hemorrhage[J].Mol Ther,2025,3 3(10):5212-5230.DOI:10.1016/j.ymthe.2025.06.034.
[57]Staecker H,Jokovic G,Karpishchenko S,et al.Efficacy and safety of AM-111 in the treatment of acute unilateral sudden deafness-a double-blind,randomized,placebo-controlled phase 3 study[J].Otol Neurotol,2019,40(5):584-594.DOI:10.1097/MAO.0000000000002229.
[58]Mukherjea D,Ghosh S,Bhatta P,et al.Early investigational drugs for hearing loss[J].Expert Opin Invest D rugs,2015,24(2):201-217.DOI:10.1517/13543784.2015.960076.
[59]Rommelspacher H,Bera S,Brommer B,et al.A single dose of AC 102 restores hearing in a Guinea pig model of noise-induced hearing loss to almost prenoise levels[J].Proc Natl Acad Sci USA,2024,121(15):e2314763121.DOI:10.1073/pnas.2314763121.
[60]Braverman I,Elziere M,Komazec Z,et al.Efficacy and safety of SENS-401 in sudden sensorineural hearing loss:the AUDIBLE-S randomized placebo-controlled phaseⅡb trial[J].Am J Otolaryngol,2024,45(6):104480.DOI:10.1016/j.amjoto.2024.104480.
[61]Crowson MG,Hertzano R,Tucci DL.Emerging therapies for sensorineural hearing loss[J].Otol Neurotol,2017,38(6):792-803.DOI:10.1097/MAO.0000000000001427.
[62]Qi J,Zhang L,Tan F,et al.Preclinical efficacy and safety evaluation of AAV-OTOF in DFNB9 mouse model and nonhuman primate[J].Adv Sci(Weinh),2024,11(3):e2306201.DOI:10.1002/advs.202306201.
[63]Ren Y,Landegger LD,Stankovic KM.Gene therapy for human sensorineural hearing loss[J].Fro nt Cell Neurosci,2019,13:323.DOI:10.3 3 8 9/fncel.2019.00323.
[64]Gombert E,George M,Maire R,et al.Sudden sensorineural hearing loss:diagnosis and management in 2021[J].Rev Med Suisse,2021,17(753):1694-1700.
基本信息:
中图分类号:R764.437
引用信息:
[1]李格,张文景,张玉波.突发性耳聋的免疫炎症机制与靶向治疗新进展[J].中华耳科学杂志,2026,24(03):227-233.
基金信息:
政府资助临床医学优秀人才培养项目（ZF2023140）
2026-03-06
2026-03-06