应用顺铂建立C57小鼠感音神经性聋模型的实验研究

Establishment of sensorineural deafness model in C57 mice by cisplatin

目的探讨顺铂诱发C57小鼠感音神经性聋模型的制备方法。方法将C57BL/6J小鼠随机分成4组,A组:耳蜗圆窗龛生理盐水给药5μL;B组:耳蜗圆窗龛顺铂给药5μL(1 mg/mL);C组:经鼓膜中耳腔顺铂给药10μL/d×5 d(1 mg/mL);D组:腹腔注射顺铂6 mg/(kg·d)×5 d。用全频程脑干听觉诱发电位(ABR)检测4个组动物的听觉反应阈为指标,以动物各频率听觉反应阈上升≥10 dB定为听力减退,并通过异硫氰酸荧光素(FITC)标记的鬼笔环肽染色观察用药后毛细胞的形态学变化。结果 A、C、D组ABR反应阈用药前后无明显变化(P>0.05);B组小鼠顺铂用药后48 h全频程ABR反应阈均升高(P<0.05),且毛细胞出现损伤、脱落,其损伤从顶回到底回有逐渐加重的趋势,外毛细胞较内毛细胞损伤严重。结论圆窗龛给药途径是建立顺铂诱发C57小鼠耳聋模型的有效途径。

Objective To establish a cisplatin-induced sensorineural deafness model in C57 mice. Methods C57BL/6J mice were divided randomly into four groups：group A （5 μL normal saline injected into the round window niche）, group B （5 μLcisplatin （1 mg/mL） injected into the round window niche）, group C （10 μL cisplatin （1 mg/mL） in- jected daily into middle ear cavity for 5 days ）, and group D （ cisplatin （6 mg/kg） injected daily into the abdominal cavity for 5 days）. 10 dB increase or above in the reaction threshold of whole octave band auditory brainstem response （ABR） was to define the decline of the heating capacity. The stereocilia and cuticular plate of hair cells stained with fluorescent phalloidin were observed. Results In group A, C and D, the whole octave band ABR reaction thresholds showed no difference before and after the administration （ P 〉 0.05 ）. However, the reaction threshold were all elevated 48 h after the administration in B group （ P 〈 0.05 ）. Meanwhile, in group B, outer hair cell （OHC） lesions were more severe than those of inner hair cell （ IHC）, and the hair cells lesions aggravated gradually from the base to apex of chochlea. Conclusion The administration of cisplatin through the window niche is the effective method to establish sensorineural deafness model in C57 mice.