山东大学耳鼻喉眼学报 ›› 2024, Vol. 38 ›› Issue (4): 22-27.doi: 10.6040/j.issn.1673-3770.0.2023.200

• 论著 • 上一篇    

盐酸氯米帕明保护听觉毛细胞免受新霉素诱导的损伤

周静1,毕秀丽2,肖雨3,胡俊4,付小龙2,于亚峰1   

  1. 1.苏州大学附属第一医院 耳鼻咽喉头颈外科, 江苏 苏州 215006;
    2.山东第一医科大学 科技创新中心, 山东 济南 250117;
    3.山东大学 生命科学学院, 山东 济南 250100;
    4.温州医科大学附属第一医院 耳鼻咽喉头颈外科, 浙江 温州 325035
  • 发布日期:2024-07-09
  • 通讯作者: 付小龙. E-mail:fuxiaolongshifan@163.com

Clomipramine hydrochloride protects auditory hair cells from neomycin-induced damage

ZHOU Jing1, BI Xiuli2, XIAO Yu3, HU Jun4, FU Xiaolong2, YU Yafeng1   

  1. 1. Department of Otorhinolaryngology & Head and Neck Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, China2. Science and Technology Innovation Center, Shandong First Medical University, Jinan 250117, Shangdong, China3. College of Life Sciences, Shandong University, Jinan 250100, Shangdong, China4. Department of Otorhinolaryngology & Head and Neck Surgery, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China
  • Published:2024-07-09

摘要: 目的 筛选出能有效抑制新霉素导致的毛细胞系(HEI-OC1)细胞死亡的小分子药物,并在小鼠耳蜗外植体和斑马鱼侧线毛细胞中进行验证。 方法 通过Cell Counting Kit-8(CCK8)计算细胞存活率来筛选出对新霉素导致的HEI-OC1细胞系死亡有保护作用的小分子药物;通过免疫荧光染色的方法在小鼠耳蜗外植体和斑马鱼侧线毛细胞中进行验证。 结果 在筛选的350种小分子药物发现能显著提高新霉素处理的HEI-OC1的细胞中存活率的药物—盐酸氯米帕明;在耳蜗外植体及斑马鱼侧线毛细胞中发现盐酸氯米帕明对新霉素导致的毛细胞死亡有保护作用。 结论 盐酸氯米帕明作为FDA批准的临床用药一定程度缓解了新霉素导致的毛细胞死亡,说明其对新霉素导致的毛细胞死亡有一定的保护作用。

关键词: 新霉素, 氨基糖苷类, 毛细胞, 盐酸氯米帕明, 耳聋

Abstract: Objective The aim of this study was to identify small-molecule drugs that inhibit neomycin-induced hair-cell-like cell(HEI-OC1)death, and to verify their effects on hair cells in cochlear explants and the lateral line of zebrafish. Methods Small-molecule drugs that increased the viability of HEI-OC1 cells were identified using Cell Counting Kit-8. The protective effect of the identified small-molecule drugs was verified in hair cells of cochlear explants and zebrafish by Immunofluorescence staining. Results Of the 350 small-molecule drugs screened, clomipramine hydrochloride was found to significantly improve the survival rate of neomycin-treated HEI-OC1 cells. In addition, clomipramine hydrochloride was found to have a protective effect on hair cells of neomycin-treated mouse cochlear explants and the lateral line of zebrafish. Conclusion Clomipramine hydrochloride, which as an FDA-approved clinical drug, has a protective effect against neomycin-induced hair cell damage.

Key words: Neomycin, Aminoglycosides, Hair cells, Clomipramine hydrochloride, Deafness

中图分类号: 

  • R764.43
[1] Prasad KN, Bondy SC. Increased oxidative stress, inflammation, and glutamate: potential preventive and therapeutic targets for hearing disorders[J]. Mech Ageing Dev, 2020, 185: 111191. doi:10.1016/j.mad.2019.111191
[2] 丘春柳. 舍曲林对强迫症患者临床症状、执行功能和职业功能的远期效果 [J]. 中华行为医学与脑科学杂志,2014,23(6): 507-510. doi: 10.3760/cma.j.issn.1674-6554.2014.06.009
[3] He ZH, Sun S, Waqas M, et al. Reduced TRMU expression increases the sensitivity of hair-cell-like HEI-OC-1 cells to neomycin damage in vitro[J]. Sci Rep, 2016, 6: 29621. doi:10.1038/srep29621
[4] Zhou MJ, Sun GY, Zhang LL, et al. STK33 alleviates gentamicin-induced ototoxicity in cochlear hair cells and House Ear Institute-Organ of Corti 1 cells[J]. J Cell Mol Med, 2018, 22(11): 5286-5299. doi:10.1111/jcmm.13792
[5] Kalinec GM, Webster P, Lim DJ, et al. A cochlear cell line as an in vitro system for drug ototoxicity screening[J]. Audiol Neurotol, 2003, 8(4): 177-189. doi:10.1159/000071059
[6] He ZH, Sun S, Waqas M, et al. Reduced TRMU expression increases the sensitivity of hair-cell-like HEI-OC-1 cells to neomycin damage in vitro[J]. Sci Rep, 2016, 6: 29621. doi:10.1038/srep29621
[7] Kalinec G, Thein P, Park C, et al. HEI-OC1 cells as a model for investigating drug cytotoxicity[J]. Hear Res, 2016, 335: 105-117. doi:10.1016/j.heares.2016.02.019
[8] Yang QQ, Zhou YW, Yin HY, et al. PINK1 protects against gentamicin-induced sensory hair cell damage: possible relation to induction of autophagy and inhibition of p53 signal pathway[J]. Front Mol Neurosci, 2018, 11: 403. doi:10.3389/fnmol.2018.00403
[9] Zhou MJ, Sun GY, Zhang LL, et al. STK33 alleviates gentamicin-induced ototoxicity in cochlear hair cells and House Ear Institute-Organ of Corti 1 cells[J]. J Cell Mol Med, 2018, 22(11): 5286-5299. doi:10.1111/jcmm.13792
[10] Ogier JM, Burt RA, Drury HR, et al. Organotypic culture of neonatal murine inner ear explants[J]. Front Cell Neurosci, 2019, 13: 170. doi:10.3389/fncel.2019.00170
[11] Nadol JB Jr. Hearing loss[J]. N Engl J Med, 1993, 329(15): 1092-1102. doi:10.1056/nejm199310073291507
[12] Forge A, Schacht J. Aminoglycoside antibiotics[J]. Audiol Neurotol, 2000, 5(1): 3-22. doi:10.1159/000013861
[13] Yumi Sugimoto, et al. The tricyclic antidepressant Clomipramine increases plasma glucose levels of mice[J]. Pharmacol Sci, 2003,93(1):74-79.doi: 10.1254/jphs.93.74
[14] Berton O, Nestler EJ. New approaches to antidepressant drug discovery: beyond monoamines[J]. Nat Rev Neurosci, 2006, 7(2): 137-151. doi:10.1038/nrn1846
[15] Mushtaq Ahmed. Comparative study of the inhibitory effect of antidepressants on cholinesterase activity in Bungarus sindanus(krait)venom, human serum and rat striatum[J]. Enzyme Inhib Med Chem, 2008,23(6):912-7.doi: 10.1080/14756360701809977
[16] Cavaliere F, Fornarelli A, Bertan F, et al. The tricyclic antidepressant clomipramine inhibits neuronal autophagic flux[J]. Sci Rep, 2019, 9(1): 4881. doi:10.1038/s41598-019-40887-x
[17] Yao Q, DeSmidt AA, Tekin M, et al. Hearing assessment in zebrafish during the first week postfertilization[J]. Zebrafish, 2016, 13(2): 79-86. doi:10.1089/zeb.2
[18] Riley BB, Moorman SJ. Development of utricular otoliths, but not saccular otoliths, is necessary for vestibular function and survival in zebrafish[J]. J Neurobiol, 2000, 43(4): 329-337. doi:10.1002/1097-4695(20000615)43: 4<329: aid-neu2>3.0.co;2-h
[19] Sun P, Zhang YL, Zhao F, et al. An assay for systematically quantifying the vestibulo-ocular reflex to assess vestibular function in zebrafish larvae[J]. Front Cell Neurosci, 2018, 12: 257. doi:10.3389/fncel.2018.00257
[20] Tanya T Whitfield, Bruce B Riley, et al. Development of the zebrafish inner ear[J]. Dev Dyn, 2002,223(4):427-458.doi: 10.1002/dvdy.10073
[21] Ghysen A, Dambly-Chaudière C. The lateral line microcosmos[J]. Genes Dev, 2007, 21(17): 2118-2130. doi:10.1101/gad.1568407
[22] Zhong ZH, Fu XL, Li H, et al. Citicoline protects auditory hair cells against neomycin-induced damage[J]. Front Cell Dev Biol, 2020, 8: 712. doi:10.3389/fcell.2020.00712
[23] Zheng ZW, Tang DM, Zhao LP, et al. Erratum to “liproxstatin-1 protects hair cell-like HEI-OC1 cells and cochlear hair cells against neomycin ototoxicity”[J]. Oxid Med Cell Longev, 2021: 9873282. doi:10.1155/2021/9873282
[24] Miyoshi H, Otomo M, Takahashi K. Clomipramine inhibits dynamin GTPase activity by L-α-phosphatidyl-L-serine stimulation[J]. J Biochem, 2023, 174(3): 267-272. doi:10.1093/jb/mvad038
[1] 李为,赵毅,葛玥铭,付洪涛,王进东,张晓龙,董洁,程钰翔. 新生儿常见耳聋基因突变热点及对听力的影响[J]. 山东大学耳鼻喉眼学报, 2024, 38(1): 1-8.
[2] 许海艳,曹卫,范大川. 多元复合声治疗对突聋患者耳鸣的疗效分析[J]. 山东大学耳鼻喉眼学报, 2023, 37(4): 38-45.
[3] 周加敏,宋玉婉,孙岩. 细胞焦亡在老年退行性疾病中的研究进展[J]. 山东大学耳鼻喉眼学报, 2023, 37(4): 172-180.
[4] 李聪,李玲,刘亭彦, 陈良. 氨基糖苷类抗生素耳毒性影响因素研究进展[J]. 山东大学耳鼻喉眼学报, 2023, 37(2): 128-134.
[5] 杨琨, 陈利娟, 何小丹, 刘志奇, 沙素华. 卡那霉素和2-羟丙基-β-环糊精耳毒性的比较研究[J]. 山东大学耳鼻喉眼学报, 2022, 36(4): 6-11.
[6] 张艳红, 李娟娟, 曾宪海, 缑灵山, 王朝霞, 魏建芳, 马芳, 邱书奇. 耳聋基因panel在耳聋基因诊断中的临床应用[J]. 山东大学耳鼻喉眼学报, 2022, 36(4): 27-34.
[7] 石安妮,张佳佳,白鹏,张重阳. 浅析“颈部七线法”针刺治疗突发性耳聋的内涵[J]. 山东大学耳鼻喉眼学报, 2022, 36(4): 103-107.
[8] 李祯,崔丽梅,孙岩. 骨形态发生蛋白4在内耳发育及在毛细胞与螺旋神经节细胞再生中的研究进展[J]. 山东大学耳鼻喉眼学报, 2022, 36(2): 108-112.
[9] 钟丽萍,官希龙,王晶晶,汤勇. 鼓室与全身应用激素治疗突发性耳聋的系统评价与Meta分析[J]. 山东大学耳鼻喉眼学报, 2021, 35(5): 1-10.
[10] 林育珊,卢标清. 从心脾论治突发性耳聋的疗效观察[J]. 山东大学耳鼻喉眼学报, 2020, 34(6): 6-11.
[11] 梁敏,吴悔,陈建勇,张勤,李姝娜,郑贵亮,何景春,陈向平,杨军. 前庭诱发肌源性电位预测突聋患者疗效的临床价值[J]. 山东大学耳鼻喉眼学报, 2020, 34(5): 27-32.
[12] 吴悔,梁敏,陈建勇,张勤,李姝娜,郑贵亮,何景春,陈向平,杨军. 全聋型突发性耳聋患者的预后与前庭症状及前庭功能关系的回顾性分析[J]. 山东大学耳鼻喉眼学报, 2020, 34(5): 33-38.
[13] 徐丽娜,高艳慧,何双八. 南京地区耳聋患者常见耳聋基因突变的分析[J]. 山东大学耳鼻喉眼学报, 2019, 33(6): 45-48.
[14] 刘军,冀飞,李万鑫. 重度-极重度感音性聋老年人人工耳蜗植入的初步探讨[J]. 山东大学耳鼻喉眼学报, 2017, 31(5): 10-15.
[15] 王启荣, 于淑东, 古林涛. 人工耳蜗植入术前评估[J]. 山东大学耳鼻喉眼学报, 2017, 31(5): 16-18.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!