The investigation of the hypothesis, glutamate-Ca-nitric oxide (NO), in the inner ear disturbance

为探讨一氧化氮（NO）在内耳障碍中的作用，将0.5和0.1摩尔浓度的NO供体1-羟基-2-氧代-3-（3-氨丙基）-3-异丙基-1-三氮烯（NOC-5）置于豚鼠耳蜗圆窗上，观察12、28、72 h后耳蜗形态学变化。内耳毛细胞以凋亡的方式死亡，谷氨酸诱导耳蜗外毛细胞（OHC）死亡。我们研究了补充胱氨酸对耳蜗外毛细胞（OHC）变性的影响。长期暴露于谷氨酸引起的。补充胱氨酸显著减少了死亡的OHC的数量。我们研究了链霉素损伤前庭毛细胞中细胞色素c的细胞定位。提示细胞色素C的再分布参与氨基糖苷类药物诱导前庭毛细胞凋亡的途径。我们检查了豚鼠耳蜗慢性暴露于GLU后，以评估Corti器官的退化。与此同时，NO合酶（NOS）的活性被证明。GLU处理引起OHC的时间依赖性变性，同时Corti器官中NOS活性暂时增加。我们用烟酰胺腺嘌呤二核苷酸磷酸-黄递酶染色法监测链霉素作用下豚鼠前庭上皮细胞变性过程中NOS活性的变化。在受影响的上皮细胞中观察到NUS活性以剂量和时间依赖性方式增加，并且NOS抑制剂可以保护毛细胞免于凋亡。放线菌酮可显著降低NOS活性和细胞凋亡的发生。提示NO参与了氨基糖苷类药物引起的前庭上皮细胞的退行性变过程。

We investigated effect of Nitric oxide (NO) in the inner ear disturbances.The two concentrations, 0.5 and 0.1 molar concentration (MC) of 1-Hydroxy-2-oxo-3-(3-aminopropyl)-3-isopropyl-1 -triazene (NOC-5) which is NO donor was placed on the round window of the guinea pig cochlea and its morphological changes were investigated at 12, 28, 72 h after the treatment. The inner ear hair cell died in the manner of apoptosis.Glu induced death of cochlear outer hair cells (OHCs). We investigated the effect of cystine supplementation on degeneration of cochlear outer hair cells (OHCs). caused by long-term exposure to Glu.. Supplementation of cystine significantly decreased the number of dying OHCs..We examined the cellular location of cytochrome c in streptomycin-damaged vestibular hair cells. suggesting that redistribution of cytochrome c is involved in the pathway of apoptosis in vestibular hair cells induced by aminoglycosides..We examined guinea pig cochleae following chronic exposure to GLU to evaluate degeneration in the organ of Corti. In parallel, NO synthase (NOS) activity was demonstrated.. GLU treatment caused time-dependent degeneration of OHCs in conjunction with a temporal increase of NOS activity in the organ of Corti..We used nicotinamide adenine dinucleotide phosphate-diapholase staining to monitor NOS activity during degeneration of guinea pig vestibular epithelia affected by streptomycin. Increased NUS activity was observed in affected epithelia in a dose- and time-dependent manner and a NOS inhibitor could protect hair cells from apoptosis. Additionally, cycloheximide significantly reduced NOS activity and the occurrence of apoptosis. These findings suggest tha NO is involved in the degenerative process of vestibular epithelia caused by aminoglycosides.