大鼠内耳拟老化模型对卡那霉素耳毒性的易感性  

Sensitivity to the ototoxicity of kanamycin of the rat model for mimetic aging in the inner ear

作　　者：胡钰娟[1] 孔维佳[1] 王琼[1] 许黎[1] 王莹[1] 韩月臣[1] 孔雯[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院耳鼻咽喉科,武汉430022

出　　处：《中华耳鼻咽喉头颈外科杂志》2008年第1期58-61,共4页Chinese Journal of Otorhinolaryngology Head and Neck Surgery

基　　金：国家杰出青年基金项目（39925035）;国家自然科学基金项目（30471878）;国家十五科技攻关计划（2004BA720A18-02）

摘　　要：目的研究大鼠内耳拟老化模型对卡那霉素的易感性。方法Wistar大鼠50只，随机分为4组，A组（半乳糖组，14只）5％D-半乳糖颈部皮下注射（150mg·kg^-1·d^-1），共8周，继以生理盐水腹腔注射10d；B组（半乳糖加卡那霉素组，14只）皮下注射半乳糖同A组，8周后，腹腔注射硫酸卡那霉素（500mg·kg^-1·d^-1）10d；C组（卡那霉素组，12只）前8周用生理盐水代替半乳糖，后10d注射卡那霉素同B组；D组（空白对照组，10只）仅给予生理盐水注射。听性脑干反应（auditory brainstem respones，ABR）检测各组大鼠反应阈，比色法检测各组大鼠膜迷路谷胱甘肽过氧化物酶（glutathione peroxidase，GSH—PX）活性。利用巢式聚合酶链式反应技术检测内耳组织线粒体DNA 4834 bp缺失突变的发生情况。结果用药后A组大鼠线粒体DNA 4834 bp缺失突变发生率为100％（28耳／28耳），B组为92．86％（26耳／28耳），C组和D组均无线粒体DNA 4834 bp缺失突变检出。A组GSH—PX活性为（59．07±8．70）U（-↑x±s，下同），B组（63．29±12．40）U，C组（136．67±9．53）U，D组（142．10±7．02）U；A组和D组之间差异具有统计学意义（P=0．000），A组和B组、C组和D组之间差异无统计学意义（P值分别为0．307和0．151）。ABR阈值（峰值等效声压级）A组平均提高（5．36±3．08）dB，B组为（61．79±11．20）dB，C组为（34．17±4．69）dB，D组为（6．50±3．37）dB；A组和D组之间差异无统计学意义（P=0．398），B组和D组、B组和C组、C组和D组之间差异具有统计学意义（P值均为0．000）。结论D-半乳糖可以诱导大鼠内耳拟老化模型，内耳组织中线粒体DNA 4834 bp缺失突变率极高，该模型对卡那霉素耳毒性的易感性增强。Objective To research the animal model with mimetic aging effect in the inner ear predispose to the ototoxicity of kanamycin. Methods Fifty wistar rats were randomly divided into four groups： group A （D-galactose group, n = 14） were treated with hypodermic 5% D-galactose （150 mg · kg^-1 · d^-1） for 8 weeks and then with intraperitoneal saline for 10 days;group B （D-galactose and kanamycin group, n = 14） were given the same dose of D-galactose but kanamycin （500 mg · kg^-1 · d^-1 ） instead of saline; group C （kanamycin group, n = 12 ） were treated with saline for 8 weeks and then with intraperitoneal kanamycin for 10 days;group D （control group, n = 10 ） were given saline only. Auditory brainstem response （ABR） was used to detect the hearing threshold of rats and colorimetry was used to analyze the activity of the GSH-PX. The inner ear tissue was harvested and the mitochondrial DNA was amplified to identify the 4834 bp deletion mutation by nested primer polymerase chain reaction （ nested PCR） technique. Results The incidence of mitochondrial DNA 4834 bp deletion mutation was 100 % （28/28） in group A, 92. 86 % （26/28） in group B and 0 % in group C or group D. The activity of GSHPX in group A was （59. 07 ± 8. 70 ） U, （ 63.29 ± 12.40 ） U in group B, （ 136. 67 ± 9. 53 ） U in group C and （142.10 ±7.02）U in group D. The difference between group A and D was significant（P = 0. 000） while the difference between group A and B was not significant（ P = 0. 307 ） ,which was similarly as between group C and group D（ P = 0. 151 ）. ABR threshold was （5.36 ± 3.08 ） dB peSPL in group A, （61.79 ± 11.20） dB peSPL in group B, （ 34. 17 ± 4. 69 ） dB peSPL in group C and （6. 50 ± 3.37 ） dB peSPL in group D. No difference was found between group A and D （ P = 0. 398 ） while the difference in shift of ABR threshold between group B and group C（ or group D） was significant（ P = 0. 000）. Conclusions The mimetic aging effect in the inne

关 键 词：半乳糖 DNA 线粒体 基因缺失 卡那霉素 

分 类 号：R686[医药卫生—骨科学]