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

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.