Development of Local Drug Therapy on the Inner Ear

我们确定了内耳局部药物治疗的研究项目。在整个项目中，使用了单侧耳蜗腔内药物注入系统的动物模型。药物输注采用渗透泵与导尿管相连，导引药物至耳蜗顶。作为对照，人工外淋巴液的输注对耳蜗无损伤。在电生理学和耳蜗细胞学方面。用卡那霉素和乙氰酸制作双侧耳蜗卡那霉素耳毒性模型，以西米米松为实验药物，对卡那霉素所致耳蜗炎有保护作用。卡那霉素给药前两天给药组比卡那霉素给药同日开始给药组的保护作用更强。另一种诱导型一氧化氮合酶抑制剂对卡那霉素诱导的创伤有保护作用。使用无特定荧光染料的附加实验。DAP-2DA实验侧卡那霉素诱导的NO合成较对照侧减少。我们还评估了对无钙外淋巴液的影响。NMDA受体拮抗剂和神经营养素的鸡尾酒，并确定其合适的浓度。

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.