利尿酸是打开血-迷路屏障的钥匙

Ethacrynic acid is the key for opening of the blood-labyrinth barrier

目的观察在不同的时机应用利尿酸以暂时破坏耳蜗血管纹上皮是否能够开放血-迷路屏障,从而促使庆大霉素进入耳蜗或者从耳蜗排出。方法听神经动作电位测试技术,全耳蜗毛细胞计数定量观察技术和荧光偏振免疫法测定庆大霉素浓度的技术被用于以下两个不同目的的实验观察。(1)当庆大霉素血中浓度高于内耳液浓度时,应用利尿酸破坏蜗管外壁以促使更多的庆大霉素进入耳蜗以制备不同程度耳蜗损害的动物模型。(2)当庆大霉素内耳浓度高于血中浓度时,应用利尿酸损坏蜗管外壁以促使蓄积在耳蜗内的庆大霉素从内耳排出以达到挽救毛细胞的目的。结果1郾当庆大霉素血中浓度高于内耳液浓度时,注射利尿酸可造成更多的毛细胞损害和听功能障碍,外淋巴中药物的峰值浓度和半衰期浓度也均比单独一次注射庆大霉素动物外淋巴中药物浓度增加一倍,说明同时注射利尿酸可促使更多的庆大霉素从血液进入耳蜗并造成更严重的毛细胞损害。2郾当血液中庆大霉素排空之后,注射利尿酸可减少毛细胞数量的损失程度,同时发现延迟注射利尿酸组动物的听力损失程度比不经利尿酸处理动物组有所减轻,外淋巴中药物浓度也比不经利尿酸处理动物组降低一半,说明当GM在耳蜗内蓄积但血清中已经排空时注射EA有助于降低药物在耳蜗内的蓄积并挽救尚未被破坏的毛细?

Objective To observe whether ethacrynic acid (EA) induced temporal damage to stria vascularis may potentiate gentamicin (GM) ototoxicity at a time when the concentration of GM in the blood is high, may also rescue hair cells from GM damage by permitting efflux of GM from the cochlear fluids into the blood stream at a time when the concentration of GM in the blood is low. Methods Cochlear action potentials, cochlear hair cell counts, and GM concentrations in blood and perilymph were tested for the following experiments. (1) When GM level is high in blood, EA permits entry of GM into the cochlea for making models of selective cochlear hair cell damage. (2) When GM level is low in blood, EA permits efflux of GM from the cochlear fluids for rescue of cochlear hair cells. Results (1) When the GM concentration is higher in blood serum, EA injection enhances GM concentration in perilymph, and causes significantly more hearing loss and hair cell loss. (2) When the GM concentration is higher in cochlear fluids, EA injection reduces GM concentration in perilymph, and rescues hair cell loss from GM damage. Conclusion EA is the key for opening of the blood-labyrinth barrier.