摘要
目的 观察聚天冬氨酸 (polyasparticacid ,PAA)对庆大霉素 (gentamicin ,GM)致耳蜗组织氧自由基产生的影响 ,进一步探讨PAA对GM耳毒性拮抗作用机制。方法 将 88只豚鼠随机分为Ⅰ组 单用GM、Ⅱ组 PAA +GM、Ⅲ组 单用PAA、Ⅳ组 单用生理盐水 ,采用电子顺磁共振法 (electronparamagneticresonancespectroscopy ,EPR) ,直接探测在体给药 1、5、10d后 ,豚鼠耳蜗组织羟自由基(OH-)的产生量 ;同时 ,记录ABR ,用透射电镜观察耳蜗Corti器毛细胞溶酶体形态改变。结果 ①给药 1dⅠ、Ⅱ组耳蜗组织EPR积分值有升高趋势 ;ABR阈值 4组间差异无显著性 (P >0 .0 5 ) ;耳蜗Corti器毛细胞溶酶体形态无明显改变。②给药 5dⅠ组耳蜗组织EPR积分值 (37.74± 4.10 )较其他 3组明显升高 (P <0 .0 1) ,给药 10d 4组间耳蜗组织EPR积分值差异无显著性 (P >0 .0 5 ) ;超微结构Ⅰ组耳蜗Corti器毛细胞皮板下溶酶体改变给药 10d较给药 5d更明显 ,可见溶酶体聚集数量增多 ,体积明显增大 ;Ⅰ组ABR阈值随用药时间延长而升高。结论 PAA对GM致耳蜗组织氧自由基的产生有抑制作用 。
Objective To observe the polyaspartic acid(PAA) inhibition of gentamicin induced reactive oxygen species generation in cochlea of guinea pig and to investigate the protective mechanism of polyaspartic acid on gentamicin ototoxicity. Methods Eighty eight guinea pigs were divided randomly into four groups (GM, PAA+GM, PAA, and Saline). Gentamicin induced reactive oxygen species (ROS) formation in cochlear tissue was detected directly with electron paramagnetic resonance (EPR) spectrometry at 1st, 5th and 10th day after administration of the drugs. At the same time, ABRs of guinea pigs were recorded and ultrastructural changes of lysosomes in the cochlear hair cells were observed with transmission electron microscopy. Results ①At 1st day after administration of PAA and GM, there was some increase in EPR spectrometry in group GM and PAA+GM, There was no significant difference of ABR thresholds and ultrastructural changes of lysosomes in the cochlear hair cells among four groups( P >0.05). ②At 5th day, there was significant increase in of EPR spectrometry in group I (37.74±4.10, P <0.01). At 10th day after administration of PAA and GM, there was no significant difference in EPR spectrometry among four groups ( P >0.05). In GM group, ultrastructural changes of lysosomes beneath cuticular plate of cochlear hair cells were more significant at 10th day than those at 5th day, including the increased number and volume of lysosome. In group GM, the longer the gentamicin administrated, the more significant increase in ABR thresholds had been noted. Conclusion PAA significantly inhibits gentamicin induced reactive oxygen species generation in cochlea of guinea pig, which showed that PAA has protective effect on gentamicin ototoxicity and phospholipidosis in guinea pigs.
出处
《中华耳鼻咽喉科杂志》
CSCD
北大核心
2001年第4期267-270,T003,共5页
Chinese Journal of Otorhinolaryngology
关键词
听力障碍
自由基
天冬氨酸
氨基糖苷抗生素类
庆大霉素
耳毒性
电子顺磁共振法
Hearing disorders
Free radicals
Aspartic acid
Antibiotics, aminoglycoside
Gentamicin(GM) Electron paramagnetic resonance spectroscopy