N-乙酰半胱氨酸对庆大霉素耳蜗损伤的保护作用

目的通过建立大鼠耳毒性损伤模型,观察N-乙酰半胱氨酸(NAC)对庆大霉素所致耳蜗损伤的保护作用。方法健康Wistar大鼠60只,随机分为正常组、对照组、庆大霉素组、NAC干预-1组、NAC干预-2组。对照组腹腔注射生理盐水120 mg/(kg.d),共14 d;庆大霉素组腹腔注射硫酸庆大霉素120 mg/(kg.d),共14 d;NAC干预-1组在上述剂量腹腔注射庆大霉素前1 h腹腔注射100 g/L的NAC 350 mg/(kg.d),共14 d;NAC干预-2组注射庆大霉素(同庆大霉素组)14 d后再腹腔注射NAC 3 350 mg/(kg.d),共14 d。所有动物在实验前作听性脑干反应(ABR)阈值测定,除正常组外其他组动物分别在全部用药结束后24 h作ABR阈值测定,处死后取听泡,苏木精-伊红染色法观察耳蜗各部的组织学改变;免疫组织化学法检测耳蜗中核因子-κB(NF-κB)及肿瘤坏死因子-α(TNF-α)的表达。结果用药结束后,庆大霉素组ABR阈值与其他组比较差异均有显著性(F=74.77,q=3.28~5.29,P<0.05),NAC干预-2组与其他组比较差异均有显著性(q=2.24~3.28,P<0.05)。庆大霉素组和NAC干预-2组血管纹、螺旋神经节和Corti器毛细胞NF-κB、TNF-α表达增强,与其他组比较差异均有显著性(F=27.47~48.81,q=1.34~4.31,P<0.05)。结论NF-κB和TNF-α可能共同参与了耳蜗药物性损伤过程,NAC可能对庆大霉素所致的耳蜗损伤具有保护作用。

THE PROTECTION OF N-ACETYLCYSTEINE ON DAMAGED COCHLEA CAUSED BY GENTAMICIN

Objective To investigate the protection of N-acetylcysteine(NAC) against the damage of cochlea caused by Gentamicin by creating a rat model of ototoxicity. Methods Sixty healthy Wistar rats were randomized to five groups: the normal,control,Gentamicin ototoxicity(GO),NAC intervention-1(NACI-1) and NAC intervention-2(NACI-2) groups.To the control,peritoneal injection(PI) of normal saline 120 mg/(kg·d)] was given;to the GO,PI of Gentamicin 120 mg/(kg·d)] was offered;to the NACI-1,PI of NAC 350 mg/(kg·d)] was done one hour before PI of the same dosage of Gentamicin was given as the former two groups.The course was 14 days for the above three groups.To the NACI-2,14 days after PI of Gentamicin,same as the GO,and then PI of NAC 350 mg/(kg·d) was carried out for another 14 days.All the rats underwent ABR leak-point detection before experiment and 24 hours after ending of medication,except those in the normal group.The rats were killed and the otic vesicles collected,which were stained with hematoxylin-eosin,the histomorphology of cochlea was observed.The expression of NF-κB and TNF-α was studied immunohistochemically. Results Upon completion of medication,the difference of ABR between the GO and the other four groups(F=74.77;q=3.28-5.29;P<0.05),and that of ABR between the NACI-2 and the other four groups were significant(q=2.24-3.28,P<0.05).The expression of NF-κB and TNF-α in psalterial cord,spiral ganglion and Corti hair cell in the GO and NACI-2 was stronger than that in the other four groups(F=27.47-48.81;q=1.34-4.31;P<0.05). Conclusion NF-κB and TNF-α may involve in the course of pharmacologic damage of the cochlea caused by Gentamycin,on which NAC probably shows its protection.