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[Math1基因疗法对卡那霉素和速尿诱导的耳聋豚鼠的作用]

[Math1 gene therapy for kanamycin and furosemide-induced deaf guinea pigs].

作者信息

Zhang Xian-Fen, Yang Shi-Ming, Han Dong-Yi, Guo Wei-Wei, Sun Jian-He, Gao Ju, Sun Dong-Xiu, Sun Ai-Ling, Li Zhen, Wei Xiao-Na

机构信息

Department of Otorhinolaryngology, Yantai Hill Hospital, Yantai, China.

出版信息

Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2013 Jul;48(7):584-8.

PMID:24313209
Abstract

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.

摘要

目的

观察向卡那霉素和速尿诱导的聋性豚鼠耳蜗内注射math1基因前后耳蜗毛细胞的形态及功能变化。探讨Math1基因用于药物性耳聋治疗的可行性。

方法

对健康成年豚鼠肌内注射卡那霉素(500mg/kg)和静脉注射速尿(50mg/kg)建立耳聋模型。将听性脑干反应(ABR)阈值>95dB SPL的豚鼠随机分为五组。空白对照组(未作任何处理,n=3)、手术对照组(右耳鼓阶手术,n=3)、人工外淋巴组(右耳鼓阶注射人工外淋巴,n=3)、病毒载体组[右耳鼓阶注射携带增强型绿色荧光蛋白(EGFP)基因的腺病毒(Ad. EGFP),n=4]、Math1基因治疗组[右耳鼓阶注射携带Math1和EGFP基因的腺病毒(Ad. Math1-EGFP),n=6]。每组动物在注射前后均接受ABR测试。通过扫描电子显微镜观察耳蜗组织。

结果

不同组间短纯音(4、8、16、20kHz)的ABR阈值差异无统计学意义(P>0.05)。部分重度聋性豚鼠注射Ad. Math1-EGFP基因后毛细胞数量增加。但其他组耳蜗毛细胞的形态和数量无明显差异。

结论

向耳蜗内注射Math1基因可使药物性耳聋豚鼠的毛细胞再生或修复,但听力损失无改善。

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