Journal of Otolaryngology and Ophthalmology of Shandong University ›› 2026, Vol. 40 ›› Issue (3): 1-6.doi: 10.6040/j.issn.1673-3770.0.2025.141

• Original Article •     Next Articles

Glucocorticoids alleviate endolymphatic hydrops induced by arginine vasopressin by downregulating aquaporin-2

LI Mengxin1,2,3, XU Hui4, ZHANG Xiaoling1,2,3,5, XUE Qing1,2,3,5, JI Shuangyu1,2,3, LI Yingying6, CUI Limei1,2,3,   

  1. GUO Zhaojian7, SONG Xicheng1, 2, 3, SUN Yan1, 2, 3, CHEN Liang1, 2, 31. Department of Otorhinolaryngology & Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai 264099, Shandong, China2. Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai 264099, Shandong, China3. Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai 264099, Shandong, China4. Department of Stomatology, Yantai Yuhuangding Hospital, Qingdao University, Yantai 264099, Shandong, China5. The Second Medical College of Binzhou Medical University, Yantai 264030, Shandong, China6. Fuyang Cancer Hospital, Fuyang 236001, Anhui, China7. Department of Pathology, Yantai Yuhuangding Hospital, Qingdao University, Yantai 264099, Shandong, China
  • Published:2026-05-22

Abstract: Objective To investigate the therapeutic effect of glucocorticoids on arginine vasopressin(AVP)-induced endolymphatic hydrops(ELH)in rats and its association with the regulation of aquaporin-2(AQP2)expression. Methods Wistar rats were randomly divided into four groups: control(normal saline), model(desmopressin acetate), dexamethasone(DXM)intervention, and DXM + mifepristone(RU486)intervention groups. Cochlear tissues were collected for hematoxylin-eosin staining to assess the degree of ELH, quantified by the ratio(R value)of the scala media area to the sum of scala media and scala vestibuli areas. Immunohistochemistry was performed to analyze the distribution and expression of AQP2 protein in the cochlea, and qRT-PCR was used to detect AQP2 mRNA expression levels. Results Compared with the control group, the model group showed significant ELH(P<0.01)and markedly increased AQP2 mRNA and protein expression(P<0.05). The DXM group exhibited reduced ELH(P<0.05)and decreased AQP2 expression(P<0.05)compared with the model group. In the DXM+RU486 group, both ELH severity and AQP2 expression were significantly higher than those in the DXM group(P<0.001). Immunohistochemistry revealed widespread AQP2 expression in the stria vascularis(SV), spiral ligament(SL), organ of Corti(OC), Reissner's membrane, and spiral ganglion neurons, with predominant localization to the cell membrane. Changes in AQP2 expression in the SV and SL were consistent with the degree of hydrops. In the OC, although AQP2 expression decreased in the DXM group, the difference was not statistically significant. Conclusion Glucocorticoids may alleviate AVP-induced ELH by downregulating AQP2 expression in the cochlea, particularly in the SV and SL. This effect can be partially reversed by the glucocorticoid receptor antagonist mifepristone.

Key words: Glucocorticoid, Endolymphatic Hydrops, Aquaporin-2

CLC Number: 

  • R764
[1] Hallpike CS, Cairns H. Observations on the pathology of ménière's syndrome:(section of otology)[J]. Proc R Soc Med, 1938, 31(11): 1317-1336. doi: 10.1177/003591573803101112
[2] Pender DJ. Meniere's disease: Structural considerations in early cochlea Hydrops[J]. Laryngoscope Investig Otolaryngol, 2024, 9(6): e70041. doi:10.1002/lio2.70041
[3] Thulasiram MR, Ogier JM, Dabdoub A. Hearing function, degeneration, and disease: spotlight on the stria vascularis[J]. Front Cell Dev Biol, 2022, 10: 841708. doi:10.3389/fcell.2022.841708
[4] Huang C, Wang Q, Pan XY, et al. Up-regulated expression of interferon-gamma, interleukin-6 and tumor necrosis factor-alpha in the endolymphatic sac of Meniere's disease suggesting the local inflammatory response underlies the mechanism of this disease[J]. Front Neurol, 2022, 13: 781031. doi:10.3389/fneur.2022.781031
[5] Kim SH, Kim JY, Lee HJ, et al. Autoimmunity as a candidate for the etiopathogenesis of Meniere's disease: detection of autoimmune reactions and diagnostic biomarker candidate[J]. PLoS One, 2014, 9(10): e111039. doi:10.1371/journal.pone.0111039
[6] Egami N, Kakigi A, Takeda T, et al. Type 1 allergy-induced endolymphatic Hydrops and the suppressive effect of H1-receptor antagonist(olopatadine hydrochloride)[J]. Otol Neurotol, 2014, 35(3): 104-109. doi: 10.1097/mao.0000000000000195
[7] Das S, Bakshi SS, Seepana R. Demystifying autoimmune inner ear disease[J]. Eur Arch Otorhinolaryngol, 2019, 276(12): 3267-3274. doi: 10.1007/s00405-019-05681-5
[8] Sajjadi H, Paparella MM. Meniere's disease[J]. Lancet, 2008, 372(9636): 406-414. doi: 10.1016/S0140-6736(08)61161-7
[9] Xue Q, Xing WW, Liu YX, et al. Effects of intratympanic injection of dexamethasone on endolymphatic Hydrops and changes in guinea pigs inner ear CFTR expression[J]. J Clin Otorhinolaryngol Head Neck Surg, 2014, 28(19): 1483-1486. doi: 10.13201/j.issn.1001-1781.2014.19.009
[10] Takeda T, Takeda S, Kakigi A, et al. Hormonal aspects of Ménière's disease on the basis of clinical and experimental studies[J]. ORL J Otorhinolaryngol Relat Spec, 2010, 71(1): 1-9. doi: 10.1159/000265113
[11] Maekawa C, Kitahara T, Kizawa K, et al. Expression and translocation of aquaporin-2 in the endolymphatic sac in patients with Meniere's disease[J]. J Neuroendocrinol, 2010, 22(11): 1157-1164. doi: 10.1111/j.1365-2826.2010.02060.x
[12] Gu FM, Han HL, Zhang LS. Effects of vasopressin on gene expression in rat inner ear[J]. Hear Res, 2006, 222(1/2): 70-78. doi: 10.1016/j.heares.2006.08.016
[13] Luo Y, Zhang DG, Chen YL, et al. Dexamethasone protects against arsanilic acid-induced rat vestibular dysfunction through the BDNF and JNK 1/2 signaling pathways[J]. Mol Med Rep, 2019, 19(3): 1781-1790. doi: 10.3892/mmr.2019.9835
[14] 张斯, 王林娥, 刘攀, 等. 圆窗膜挑开前后豚鼠听功能变化研究[J]. 中国听力语言康复科学杂志, 2024, 22(4): 433-437, 446. doi: 10.3969/j.issn.1672-4933.2024.04.024 ZHANG Si, WANG Line, LIU Pan, et al. Effect of opening round window membrane on auditory function of healthy guinea pigs[J]. Chinese Scientific Journal of Hearing and Speech Rehabilitation, 2024, 22(4): 433-437, 446. doi: 10.3969/j.issn.1672-4933.2024.04.024
[15] Jiang LY, He JJ, Chen XX, et al. Arginine vasopressin-aquaporin-2 pathway-mediated dehydration effects of electroacupuncture in guinea pig model of AVP-induced eendolymphatic Hydrops[J]. Chin J Integr Med, 2019, 25(10): 763-769. doi: 10.1007/s11655-017-2411-2
[16] Lundquist P G, Kimura R, Wersaell J. Experiments in endolymph circulation[J]. Acta Otolaryngol Suppl, 1964, 188: 198. doi: 10.3109/00016486409134562
[17] Takeda T, Takeda S, Kakigi A. A possible mechanism of the formation of endolymphatic Hydrops and its associated inner ear disorders[J]. Auris Nasus Larynx, 2020, 47(1): 25-41. doi: 10.1016/j.anl.2019.09.005
[18] Sun SJ, Zhang DG, Sun GY, et al. Solute carrier family 4 member 1 might participate in the pathogenesis of Meniere's disease in a murine endolymphatic hydrop model[J]. Acta Oto Laryngol, 2019, 139(11): 966-976. doi: 10.1080/00016489.2019.1663365
[19] Nishioka R, Takeda T, Kakigi A, et al. Expression of aquaporins and vasopressin type 2 receptor in the stria vascularis of the cochlea[J]. Hear Res, 2010, 260(1/2): 11-19. doi: 10.1016/j.heares.2009.09.011
[20] Frejo L, Gallego-Martinez A, Requena T, et al. Proinflammatory cytokines and response to molds in mononuclear cells of patients with Meniere disease[J]. Sci Rep, 2018, 8(1): 5974. doi:10.1038/s41598-018-23911-4.doi: 10.1038/s41598-018-23911-4
[21] Sato A, Omichi R, Maeda Y, et al. A glucocorticoid-regulating molecule, Fkbp5, may interact with mitogen-activated protein kinase signaling in the organ of Corti of mice cochleae[J]. Sci Rep, 2025, 15: 7506. doi:10.1038/s41598-025-92400-2
[22] 廖行伟, 任毅, 黄巧, 等. P38MAPK调控AQP2参与内淋巴积水的形成[J]. 中华耳科学杂志, 2022, 20(4): 605-611. doi: 10.3969/j. issn.1672-2922.2022.04.013 LIAO Xingwei, REN Yi, HUANG Qiao, et al. P38MAPK participates in formation of endolymphatic Hydrops by regulating AQP2[J]. Chinese Journal of Otology, 2022, 20(4): 605-611. doi: 10.3969/j. issn.1672-2922.2022.04.013
[23] Gao ZW, Schwieger J, Matin-Mann F, et al. Dexamethasone for inner ear therapy: biocompatibility and bio-efficacy of different dexamethasone formulations in vitro[J]. Biomolecules, 2021, 11(12): 1896. doi:10.3390/biom11121896
[24] Johns JD, Adadey SM, Hoa M. The role of the stria vascularis in neglected otologic disease[J]. Hear Res, 2023, 428: 108682. doi:10.1016/j.heares.2022.108682
[25] Terakado M, Kumagami H, Takahashi H. Distribution of glucocorticoid receptors and 11 beta-hydroxysteroid dehydrogenase isoforms in the rat inner ear[J]. Hear Res, 2011, 280(1/2): 148-156. doi: 10.1016/j.heares.2011.05.00
[26] Froehlich MH, Lambert PR. The physiologic role of corticosteroids in menière's disease: an update on glucocorticoid-mediated pathophysiology and corticosteroid inner ear distribution[J]. Otol Neurotol, 2020, 41(2): 271-276. doi: 10.1097/mao.0000000000002467
[27] Inagaki K, Yoshida T, Kobayashi M, et al. Impact of endolymphatic Hydrops on DPOAE in subjects with normal to mild hearing loss[J]. Laryngoscope Investig Otolaryngol, 2022, 8(1): 262-268. doi: 10.1002/lio2.998
[28] Liang JY, Wang JK, Yao WJ. Hearing loss caused by hair cell lesions[J]. IEEE Trans Biomed Eng, 2025, 72(8): 2544-2554. doi: 10.1109/TBME.2025.3547059
[1] DUAN Siyu, XUE Jinmei. Research progress of histone deacetylase 2 in glucocorticoid resistance in chronic airway inflammatory diseases [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2026, 40(1): 120-126.
[2] CAO Zhengyong, LI Xiaobo. Comparison of the safety and efficacy of short-course postoperative topical glucocorticoid adjuvant therapy for eCRSwNP combined with asthma [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2025, 39(2): 43-50.
[3] WANG Zhenxiao, SHI Guanggang, HE Mingqiang, SHI Lei. Treatment options and management strategies for patients with acute laryngotracheobronchitis [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2024, 38(5): 136-144.
[4] CHEN Xingxue, ZHANG Guangling, WU Tianyi, WANG Weiwei, SUN Zhanwei, LI Shichao, WANG Guangke. Analysis of anti-IL-4Rα monoclonal antibody and endoscopic sinus surgery in the treatment of eosinophilic chronic rhinosinusitis with nasal polyps [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2024, 38(4): 43-54.
[5] LI Shuting, ZHAO Hui, SI Mingwei, CUI Wenxuan, YANG Mengyao, WANG Hong. Fungal endophthalmitis in a patient with no history of vegetative trauma: a case report and literature review [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2024, 38(2): 103-108.
[6] WANG Lixue, ZENG Yi, WANG Lixin, PENG Xianbing. Clinical observation of the effect of infiltrating Biprofen Gelatin Sponge after functional endoscopic sinus surgery [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2023, 37(5): 16-25.
[7] LI Cong, LI Ling, LIU Tingyan, CHEN Liang. Research progress on influencing factors of aminoglycoside antibiotic ototoxicity [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2023, 37(2): 128-134.
[8] WANG Qian, LIU Na, WANG Shaopeng. A case report of Leber's idiopathic stellate neuroretinitis and literature review [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2022, 36(6): 106-110.
[9] CHEN Shiqin, WEI Pingcun, HU Yunlong, HU Jinwang. Effects of three different nasal uses of glucocorticoid on mucosal outcome after endoscopic sinus surgery [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2022, 36(3): 195-201.
[10] ZHANG Yaoyao,WANG Haitao. The application of MRI technology with intratympanic gadolinium injection in the diagnosis and treatment of Meniere's disease [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2021, 35(6): 101-107.
[11] ZHONG Liping, GUAN Xilong, WANG Jingjing, TANG Yong. Intratympanic injections and systemic glucocorticoid treatment for sudden hearing loss: a systematic review and Meta-analysis [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2021, 35(5): 1-10.
[12] . Diagnostic value of electrocochleography using external auditory canal electrode in patients with Menieres disease [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2020, 34(5): 20-26.
[13] JIANG Yang, LI Ying, CUI Gen. Efficacy of 0.1% diclofenac sodium eye drops post-SMILE [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2020, 34(2): 57-60.
[14] HUANG Qiao,YIN Shihua. Correlation between endolymphatic hydrops and inner ear epithelial sodium channels and aquaporins [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2019, 33(4): 145-148.
[15] LIU Jianbo, ZHANG Huan. Phacoemulsification combined with intravitreal ranibizumab or triamcinolone acetonide injection for the treatment of cataract accompanied by diabetic macular edema [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2019, 33(2): 99-104.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!