Math1基因内耳导入后噪声性聋豚鼠听功能改变观察  

Hearing improvement of NIHL guinea pig by overexpressed Math1 gene in the cochlea

作　　者：陈伟[1,2] 郭维维[1] 胡吟燕[1] 孙建和[1] 于宁[1] 韩东一[1] 翟所强[1] 杨伟炎[1] 何志洲 杨仕明[1] 

机构地区：[1]解放军总医院耳鼻咽喉头领外科,解放军耳鼻咽喉研究所耳神经生物中心,北京100853 [2]解放军空军总医院耳鼻咽喉头颈外科,北京100142 [3]美国Creighton大学医学院生物医学系,美国Omaha68175

出　　处：《中华耳科学杂志》2009年第4期352-356,共5页Chinese Journal of Otology

基　　金：国家高技术研究发展计划(863计划)专题项目(2007AA02Z150);国家自然科学基金重点项目(30730040);国家自然科学基金海外青年学者合作基金(No.30628030);国家自然科学基金面上项目(30871398,30571017)联合资助

摘　　要：目的观察Math1基因内耳导入对噪声性聋豚鼠听功能的影响,探讨Math1基因过表达对噪声损伤耳蜗的生物学效应,为内耳基因治疗提供实验基础和理论依据。方法经脉冲噪声致聋的豚鼠45只(各频率ABR阈值均≥95dB SPL),雌雄不限,实验开始时体重250～300g。随机分为3组:Ad-Math1-EGFP组(30只);Ad-EGFP组(5只);空白组(10只)。各组豚鼠在基因转导后4周、8周分别测试双耳ABR。测试完毕后处死动物,观察听泡及耳蜗无炎性病变者记录听阈结果。结果Math1导入后4周,导入耳各频率ABR阈值低于对照耳(右耳),也低于Ad-EGFP组及空白组,平均达到85dB SPL。Math1导入后8周,导入耳各频率ABR阈值低于对照耳(右耳),也低于Ad-EGFP组及空白组,与4周时比较,进一步好转,平均达到75dB SPL。结论Math1基因内耳导入可使噪声导致全聋的豚鼠听功能部分恢复,为噪声性聋的治疗打开了新的思路和手段。Objective To evaluate the effect of adenovirus mediated Mathl gene transferring into the cochlea of noise-indueed hearing loss （NIHL） guinea pig to assess its influence on hearing and to provide experiment foundation for inner ear gene therapy. Methods Forty-five NIHL guinea pigs （audibility threshold ≥ 95 dB SPL）, with no sex limited, weight between 250 and 300 g before this experiment, were divided into three groups randomly. Thirty guinea pigs （Ad- Math1-EGFP group） were implanted with adenovirus mediated Hathl gene. Five guinea pigs （Ad-EGFP group） were implanted with enhanced green fluorescent protein （EGFP） and ten without treatment as blank group. Auditory brainstem response （ABR） thresholds were determined in all animals at 4 weeks and 8 weeks after surgery. Results The ABR threshold of the ear inoculated in the Ad-Math1-EGFP group was lower than the control ear （right ear） and the Ad-EGFP group and the blank group 4 weeks after surgery （85 dB SPL in average）. The ABR threshold of the ear inoculated in the Ad-Math1-EGFP group was lower than the control ear （right ear） and the Ad-EGFP group and the blank group 8 weeks after surgery, and better than that 4 weeks before （75 dB SPL in average）. Conclusion Math1 gene transferred into the cochlea can partially recover the hearing loss which provides a new method for NIHL therapy.

关 键 词：基因转导 噪声性聋 MATH1 豚鼠 ABR 

分 类 号：R349.8[医药卫生—基础医学] R764.433