目的探讨依达拉奉(Edaravone,Ed)对豚鼠声损伤的保护作用。方法清洁级豚鼠30只,雌雄不限,体重200~250g。随机分3组,正常对照组10只,生理盐水组10只,依达拉奉组10只。予白噪声120dBSPL,每天4h,连续4天。噪声前半小时腹腔注射依达拉奉溶液,8.0mg/kg,每天一次,持续给药到噪声完毕后一周。噪声前,噪声后即刻,第3天,第7天行听性脑干反应(ABR)检测,第8天琥珀酸脱氢酶,免疫组化,扫描电镜检测。结果噪声前,3组豚鼠ABR阈值无明显差异(P〉0.05),噪声后即刻生理盐水及依达拉奉组ABR阈值均高于正常对照组,依达拉奉组ABR阈值低于生理盐水组,差异有统计学意义(P〈O.05),3天后,依达拉奉组ABR阈值明显降低,7天后接近正常对照组,而生理盐水组则明显高于正常对照组,差异有统计学意义(P〈0.05)。正常对照组外毛细胞胞质琥珀酸脱氢酶(SDH)着色深,胞核、纤毛排列整齐;光镜下观察生理盐水组底转毛细胞中SDH着色浅,细胞肿胀不规则,依达拉奉组较生理盐水组外毛细胞胞质着色深,细胞形态规则,免疫组化及扫描电镜检测显示正常对照组细胞核纤毛排列整齐,未见缺失,而生理盐水组和依达拉奉组底转毛细胞出现缺失,依达拉奉组较生理盐水组细胞核及纤毛缺失明显减轻。结论结合之前的实验研究,初步推测依达拉奉对噪声性耳聋中产生的自由基具有清除作用。
Objective To study effects of edaravone in preventing and protecting noise-induced hearing loss. Methods Thirty guinea pigs were randomly divided into 3 groups to receive no treatment,trearment with normal saling or treatment with edaravone given intrapertoneally at half an hour before noise exposure and for a week at 8.0mg/Kg,White niose (120dB SPL peak) were deliv- ered as noise exposure 4 hours for 4 days. Immediately after exposure to white noise and days 3,7following exposure, auditory brain- stem response(ABR) thresholds were measured.Outer hair cell morphological changes and succinate dehydrogenase(SDH) activity, immunohistochemical and scanning electron microscopy examined on Day 8 post-exposure. Results Three groups guinea pigs ABR threshold were no significant difference before exposnred(P〉O.05). Immediately after the noise, the saline group and edara- vone group ABR thresholds were higher than the normal control group, edaravone group ABR threshold was lower than the saline group(P〈0.05). Three days later, edaravone group ABR threshold was significantly reduced and closed to the normal control group until 7 days,while the saline group was significantly higher than the control group, the difference was statistically significant (P 〈 O.05).In the normal control group, there was deep SDH staining in the outer hair cells cytoplasmic ,and the nuclei and stereocilia ar- ranged in neat rows.Microscopy showed basement basal turn little SDH staining,cell swelling and irregular cell arrangement in the physiological saline treated animals.Whereas in the edaravone treated animals,there was deep SDH staining with signicantly re- duced cell and more regular cellular arrangement compared to physiological saline treated group. Mmunohistoehemistry and scan- ning electron microscopy showed that normal control group hair cell and stereocilia arranged in neat rows,edaravone group hair cell and stereocilia loss were significantly less than the saline group. Conclusions Combined with previous e