Development of Local Drug Therapy on the Inner Ear

我们制定了内耳局部药物治疗的研究项目。整个项目采用单侧耳蜗输注系统的动物模型。药物输注采用渗透泵连接导管将药物导入耳蜗。作为对照研究，人工淋巴周围输注没有对耳蜗造成损伤。在电生理学和耳蜗细胞学上。用卡那霉素和乙酸对双耳蜗建立耳毒性模型。作为实验药物，环塞米松对卡那霉素引起的耳蜗耳毒性有保护作用。在卡那霉素给药前2天输注药物组比在卡那霉素给药当天开始输注药物组的保护作用更大。另一种药物iNOS抑制剂对卡那霉素所致损伤的保护作用减弱。使用NO特异性荧光染料进行附加实验。与对照组相比，DAP-2DA在实验侧显示卡那霉素诱导的NO合成减少。我们还评估了对游离钙淋巴周围溶液的影响。NMDA受体拮抗剂和鸡尾酒神经营养因子，并确定其适当浓度。

We set the researching project regarding to the local drug therapy on the inner ear. On the entire project, an animal model with drug-infusing system to the unilateral cochlea was used. Drug infusion was perfonned with an osmotic pump connecting to catheter which lead drug to the cochiear scala tynlpani. Infusion of artificial perilymph as a control study demonstrated no damage of cochlea. in both electrophysiology and cochlear cytology. Ototoxicity modei was made with kanamycin and ethacrynic acid on the bilaterai cochlea.As an experimental agent, ciexamethasone showed protective effect, against kanamycin-induced ototoxicity in the cochlca. The group of drug infusion two days prior to kanamycin admininistration led more protective effect than the group of drug infusion started the same day as kanamycin adrninistration. The other agent, iNOS inhibitor sbowed the protective effect on the kanamycin- induced trauma. Additional experimcnt using NO specific fluoresccnt dye. DAP-2DA showed reduction of kanamycin-induced NO synthesis on experirncntal side comparing to that on control side. We have also evaluated the effects on calcium free periiymphatic solution. NMDA receptor antagomst and cocktail of neurotrophirls, and determined their adequate concentrations.