Ruan R S, Leong S K, Yeoh K H
Department of Otolaryngology, National University Hospital, Singapore.
Hear Res. 1997 Dec;114(1-2):169-78. doi: 10.1016/s0378-5955(97)00159-7.
Nitric oxide (NO) not only has normal physiological roles like vasodilation and neurotransmission in the living organism, it could also have possible neurodestructive effects under certain pathological conditions. The present study aimed to determine whether direct exposure of guinea pig cochlea to a NO donor like sodium nitroprusside (SNP), or a nitric oxide synthase (NOS) inhibitor like N(G)-nitro-L-arginine methyl ester (L-NAME), would cause damage to the auditory hair cells. A piece of gelfoam was placed on the round window of the right ear of adult albino guinea pigs. It was then soaked with 0.1 ml of SNP (3.4 microM), 0.1 ml of L-NAME (9.3 microM or 18.5 microM) or 0.1 ml of injection water, the vehicle used to dissolve the above chemicals. Twelve animals receiving SNP were perfused 1 day, 2, 3 and 7 days later, with three animals being used for each survival period. Six animals receiving L-NAME were allowed to survive up to 7 days before perfusion. Eight animals receiving injection water or 0.45% saline were used as controls. With the scanning electron microscope, the inner and outer hair cells were counted over a 1 mm length of the basilar membrane in each turn of every cochlea. The results showed that, in animals treated with L-NAME at both concentrations stated, no significant loss of either inner or outer hair cells was noted in any part of the cochlea studied. However, as early as 1 day after SNP treatment, a striking loss of inner and outer hair cells was observed in the three lower turns of the cochlea. Damage to the outer hair cells was extended to the apical turn with increasing survival period, but no significant loss of inner hair cells was evident in the apical turn at any of the survival periods studied. To rule out the possibility that the effects were due to the presence of cyanide, a metabolite of SNP, hydroxycobalamin was introduced into the scala tympani of three animals through a cannula-osmotic pump device during SNP treatment. There was no significant difference in the results between the groups with and without hydroxycobalamin infusion 7 days after SNP treatment. The present study suggests that an excessive production of NO in the inner ear could lead to extensive loss of hair cells.
一氧化氮（NO）不仅在生物体内具有血管舒张和神经传递等正常生理作用，在某些病理条件下它还可能具有神经破坏作用。本研究旨在确定将豚鼠耳蜗直接暴露于硝普钠（SNP）这种NO供体或N（G）-硝基-L-精氨酸甲酯（L-NAME）这种一氧化氮合酶（NOS）抑制剂是否会对听觉毛细胞造成损伤。将一片明胶海绵置于成年白化豚鼠右耳的圆窗上。然后用0.1毫升SNP（3.4微摩尔）、0.1毫升L-NAME（9.3微摩尔或18.5微摩尔）或0.1毫升注射用水（用于溶解上述化学物质的溶剂）浸泡。接受SNP处理的12只动物在1天、2天、3天和7天后进行灌注，每个存活期使用3只动物。接受L-NAME处理的6只动物在灌注前存活7天。接受注射用水或0.45%盐水的8只动物用作对照。使用扫描电子显微镜，在每个耳蜗的每一圈基底膜1毫米长度上对内外毛细胞进行计数。结果表明，在使用上述两种浓度L-NAME处理的动物中，在所研究的耳蜗任何部位均未观察到内毛细胞或外毛细胞有明显损失。然而，早在SNP处理后1天，在耳蜗的三个较低转中就观察到内毛细胞和外毛细胞显著损失。随着存活期延长，外毛细胞的损伤扩展到顶转，但在所研究的任何存活期，顶转内毛细胞均未出现明显损失。为排除这些效应是由于SNP的代谢产物氰化物所致的可能性，在SNP处理期间通过套管渗透泵装置将羟钴胺引入三只动物的鼓阶。SNP处理7天后，输注和未输注羟钴胺的组之间结果无显著差异。本研究表明，内耳中NO的过量产生可能导致毛细胞大量损失。
