免疫性内耳病模型的建立及地塞米松圆窗和全身给药的疗效

目的建立免疫性内耳病模型,并初步比较地塞米松圆窗局部给药和全身给药治疗的效果。方法先用钥孔嘁血蓝蛋白(KLH)加完全弗氏佐剂在豚鼠背部多点皮内注射,2周后用KLH加不完全弗氏佐剂加强,同日通过手术将浸满KLH的小块明胶海绵置于圆窗上制作免疫诱导的内耳病模型。在此基础上使用微渗透泵(同时设PBS对照组)圆窗给药,以腹腔注射全身给药治疗免疫性内耳病,给药前后听性脑干反应(ABR)测试比较治疗效果。结果①动物模型ABR听阈:6只对照组豚鼠无明显听力损失,39只实验组豚鼠听力损失在10 dB以上的有22只;②治疗效果比较:17只听力损失≥15 dB的豚鼠模型随机分为三组:圆窗局部给药6只动物,治疗全部有效,ABR听阈平均下降13.3 dB;全身给药6只动物,4只有效,ABR听阈平均下降13.7 dB;PBS组全部无效。结论KLH经圆窗诱导的免疫性内耳病模型的成功率较高;地塞米松跨圆窗给药的有效性不亚于全身给药。

Model of immune-mediated inner ear disease and efficacy of dexamethasone by systemic application or round window administration

Objective To establish a model of immune-mediated inner ear disease(IMIED) and to compare the efficacy of dexamethasone between systemic application and round window adminstration. Methods The guinea pigs were injected with keyhole limpet hemocyanin(KLH) mixed with complete Freund's adjuvant subcutaneouly in the back,and were boosted with KLH mixed with incomplete Freund's adjuvant two weeks later.Meanwhile,a small piece of gelatin sponge full of KLH was delivered on the round window through operation.Thus established a model of IMIED.Micro-osmotic pumps were used to deliver dexamethasone through the round window(PBS control group also set),and systemic application was implemented by intraperitoneal injection.The efficacy was compared by recording auditory brain-stem response(ABR) before and after the treatment. Results None of the 6 guinea pigs in the control group experienced significant hearing loss,while 22 of the 39 guinea pigs in the experiment group suffered from hearing loss beyond 10 dB.Seventeen guinea pigs with hearing loss no less than 15 dB were divided into three groups randomly and were given different treatment.Those(n=6) treated by local application through the round window enjoyed the efficacy and the mean ABR threshold decreased 13.3 dB.Four out of the 6 treated by systemic application enjoyed the efficacy and the mean ABR threshold decreased 13.7 dB.No efficacy was observed in the PBS group. Conclusion The model of IMIED can be successfully induce by KLH through the round window,and dexamethasone administered through the round window is as efficacious as systemic application.