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卡那霉素联合速尿致聋豚鼠的Math1基因治疗

ISSN号：1673-0860
期刊名称：《中华耳鼻咽喉头颈外科杂志》
时间：0
分类：R978.1[医药卫生—药品;医药卫生—药学]
作者机构：[1]山东省烟台市烟台山医院耳鼻咽喉科,264001, [2]解放军总医院耳鼻咽喉头颈外科耳鼻咽喉科研究所
相关基金：国家973计划重大科学研究计划干细胞项目（2012CB967900）;国家973计划重大科学问题导向项目（2011CBA01000）;国家863计划专题项目（2007AA022150）;国家自然科学基金重点项目（30730040）

作者：张贤芬[1], 杨仕明[2], 韩东一[2], 郭维维[2], 孙建和[2], 高举[1], 孙东绣[1], 孙爱玲[1], 李臻[1], 魏晓娜[1]

关键词：基因疗法, 碱性螺旋-环-螺旋转录因子类, 耳蜗, 听觉丧失, 感音神经性, 豚鼠, Gene therapy, Basic helix-loop-helix transcription factors , Cochlea , Hearingloss, sensorineural, Guinea pigs

中文摘要：

目的观察卡那霉素和速尿联合致聋豚鼠耳蜗鼓阶导入Math1基因后的形态学及功能改变,探讨Mathl基因治疗药物中毒性耳聋的可行性.方法健康成年豚鼠经硫酸卡那霉素（500 mg/kg）和速尿（50 mg/kg）联合致聋,将听性脑干反应（ABR）反应阈＞95 dB SPL的豚鼠按随机数字表法分为空白对照组（不做任何处置,3只）,手术对照组（右耳单纯鼓阶钻孔,3只）,人工外淋巴液组（右耳鼓阶钻孔导入人工外淋巴液,3只）,单纯病毒载体组[右耳鼓阶钻孔导入携带增强型绿色荧光蛋白基因（enhanced green fluorescent protein,EGFP）的重组腺病毒（Ad.EGFP）,4只]、Math1基因治疗组[右耳鼓阶钻孔导入携带Math1及EGFP基因的重组腺病毒（Ad.Math1-EGFP）,6只].各组动物分别于鼓阶注射前及注射后8周时行ABR测试,结束测试后处死动物,取出耳蜗组织行扫描电镜观察.结果各组豚鼠不同频率（4、8、16、20 kHz）短纯音ABR阈值在不同检测时间段差异均无统计学意义,组间比较差异亦无统计学意义（P值均＞0.05）.除Math1基因治疗组外,其余各组右耳耳蜗各回毛细胞形态和数目与左耳（自身对照）比较无明显差别.4只Math1基因治疗组豚鼠中,有2只右耳耳蜗第三回内、外毛细胞数量明显比左耳多,其中内毛细胞排列形态较外毛细胞整齐.结论鼓阶显微注射导入Math1基因能使部分卡那霉素和速尿联合致聋豚鼠的耳蜗毛细胞修复或再生,但其听觉功能没有改善.

英文摘要：

Objective To observe the morphology and function changes of cochlear hair cells before and after math1 gene injection into the cochlea of deaf guinea pigs which were induced by kanamycin and furosemide.To explore the feasibility of Math1 gene for medicine-induced deafness therapy.Methods Kanamycin（500 mg/kg） and furosemide（50 mg/kg） were given to the healthy adult guinea pigs intramuscularly and intravenously to establish the deafness model.The guinea pigs whose auditory brainstem response （ABR） threshold 〉 95 dB SPL were randomly divided into five groups.Blank control group （without any treatment,n =3）,operation control group （right ear scala tympani operation,n =3）,artificial perilymph group （right ear scala tympani injection artificial perilymph,n =3）,virus vector group [right ear scala tympani injection adenovirus which carrying enhanced green fluorescent protein（EGFP） gene （Ad.EGFP）,n =4],Math1 gene therapy group [right ear scala tympani injection adenovirus which carrying Math1 and EGFP gene（Ad.Math1-EGFP）,n =6].Each animal received ABR test before and after injection.The cochlear tissue was observed by scanning electronic microscopy.Results The ABR thresholds of tone burst（4,8,16,20 kHz） were not statistically significant in different groups （P 〉 0.05）.The number of hair cells increased in some of severe deaf guinea pigs after the injection of Ad.Math1-EGFP gene.However,there was no obvious difference with morphology and numbers of cochlea hair cells in other groups.Conclusions The injection of Math1 gene to cochlea can regenerate or repair the hair cells of medicine-induced deaf guinea pigs,but there was no improvement on the hearing loss.

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