新霉素对大鼠前庭毛细胞损伤作用的实验研究

Experiment research of neomycin damaging effect on rat vestibular hair cells

目的研究新霉素对大鼠前庭毛细胞的毒性作用,为药物性前庭功能障碍动物模型的制备和相关研究提供参考。方法将15只成年Wistar大鼠分为正常对照组(n=5)、新霉素组(n=5)和人工外淋巴液组(n=5),新霉素组大鼠在右耳通过耳蜗底转鼓阶打孔的方法在耳蜗内注入0.1%(g/100ml)新霉素5!l,人工外淋巴液组按同样方法注入人工外淋巴液5!l。正常对照组大鼠不做任何处理。处理3天后对动物进行颈髓硬膜外短声诱发电位(click-evoked potential on the surface of the cervical dura mater,CDM-CEP)检查和游泳试验以评价前庭功能;然后将动物处死,进行形态学观察。结果3天后新霉素组大鼠的前庭毛细胞即出现严重破坏,并出现严重的前庭功能损伤。正常对照组大鼠的游泳时间为(4.0±0.71)s(3～5s,n=5),新霉素组大鼠的游泳时间为(10.2±1.64)s(8～12s,n=5),人工外淋巴液组大鼠的游泳时间为(4.4±1.14)s(3～6s,n=5);在短音(click)刺激下,正常大鼠引出CDM-CEP的阈值为(85±3.54)dBSPL(80￣90dBSPL,n=5),阈值时的潜伏期为(6.59±0.41)s(6.05￣7.05s,n=5);新霉素组大鼠120dBSPL仍无法引出CDM-CEP;人工外淋巴液组大鼠引出CDM-CEP的阈值为(90±5.0)dBSPL(85￣95dBSPL,n=5),阈值时的潜伏期为(6.68±0.31)s(6.35～7.02s,n=5)。结论新霉素对大鼠前庭毛细胞具有极强的破坏作用,新霉素耳蜗内注射的方法可以制备理想的前庭功能障碍动物模型。

Objective To investigate neomycin ototoxicity in rat vestibular hair cells, and to make a pilot trial to deveelop a vestibular dysfunction animal model of ototoxicity. Methods Fifteen mature Wistar rats were divided into normal control group （n=5）, neomycin group （n=5） and artificial perilymph group （n=5）. Five μl of 0.1% （g/100 ml） neomycin was administrated to the right ear of the neomycin group rat through a hole on the scala tympani of the cochlear basal turn. The artificial perilymph group received a artificial perilymph injection in the same way. As a control, the normal group was left untreated. To evaluate animal vestibular function, the click- evoked potential on the surface of the cervical dura mater （CDM-CEP） and swimming time were recorded in all rats 3 days after neomycin treatment, and then morphologic observation were carried out after animals killed. Results Vestibular hair cell was severely destroyed and vestibular function was severely injuried in neomycin group 3 days after neomycin treatment. The swimming time is 4.0 ± 0.71 s （3-5s, n = 5） in normal control group, and 10.2 ± 1.64 s （8-12s, n = 5） in neomycin group, and 4.4 ± 1.14 s （3-6s, n = 5） in artificial perilymph group. The threshold and latency of CDM-CEP is 85 ± 3.54 dB SPL （80-90 dB, n = 5） and 6.59 ± 0.41s （6.05-7.05s, n = 5） in normal control group, and 90 ± 5.0 dB SPL（85-95 dB, n = 5） and 6.68 ± 0.31s （6.35-7.02s, n = 5） in artificial perilymph group, but CDM-CEP could not be induced even at 120 dB SPL level in neomycin group. Conclusion The neomycin possess a powerful damaging effect on vestibular hair cells of the rat. Intracochlear neomycin administration can develop an ideal vestibular dysfunction animal model.