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一氧化氮对离体耳蜗外毛细胞形态的影响:可能与感音神经性听力损失有关。

Effects of nitric oxide on morphology of isolated cochlear outer hair cells: possible involvement in sensorineural hearing loss.

作者信息

Jung Timothy T K, Llaurado Raymund J, Nam Boo Hyun, Park Seong Kook, Kim Paul D, John Earnest O

机构信息

Division of Otolaryngology-Head and Neck Surgery, Loma Linda University School of Medicine, and Jerry L. Pettis Memorial Veterans Medical Center, Loma Linda, California, USA.

出版信息

Otol Neurotol. 2003 Jul;24(4):682-5. doi: 10.1097/00129492-200307000-00025.

Abstract

HYPOTHESIS

One of the inflammatory mediators of otitis media, nitric oxide, can damage cochlear outer hair cells.

BACKGROUND

Free radicals, including nitric oxide, have been detected in middle ear effusion. Increasing evidence implicates free radicals in the pathogenesis of otitis media and possibly in the development of sensorineural hearing loss.

METHODS

Isolated outer hair cells from adult chinchilla cochlea were exposed to standard bathing solution (Control Group 1) or the nitric oxide-producing compounds, S-nitroso-N-acetyl, l-penicillamine (1-1.5 mg/ml, Experimental Group 1) or 3-morpholinosynonimine (1-1.5 mg/ml, Experimental Group 2). Since nitric oxide is readily converted to nitrite and nitrate in vivo, a second control group using sodium nitrite was used to separate potential effects of nitric oxide from nitrite (Control Group 2). All experiments were performed at an osmolality of 305 +/- 5 mOsm at room temperature, and with exposure time up to 90 minutes. The cells were observed using an inverted microscope, and the images were recorded and analyzed on the IMAGE Pro-Plus program.

RESULTS

Outer hair cells exposed to either standard bathing solution or sodium nitrite (Control Groups 1 and 2) showed no significant change in cell shape or length. Cells exposed to S-nitroso-N-acetyl and l-penicillamine or 3-morpholinosynonimine exhibited ballooning and significant shortening in mean cell length (p < 0.01).

CONCLUSION

This study demonstrates that exposure to nitric oxide causes irreversible morphologic changes in isolated outer hair cells, suggesting possible involvement of nitric oxide radical in the development of sensorineural hearing loss as a sequela of chronic otitis media.

摘要

假说

中耳炎的炎症介质之一一氧化氮可损害耳蜗外毛细胞。

背景

包括一氧化氮在内的自由基已在中耳积液中被检测到。越来越多的证据表明自由基参与了中耳炎的发病机制,并且可能与感音神经性听力损失的发生有关。

方法

将成年龙猫耳蜗分离出的外毛细胞暴露于标准浴液(对照组1)或产生一氧化氮的化合物,即S-亚硝基-N-乙酰-L-青霉胺(1-1.5mg/ml,实验组1)或3-吗啉代-synonimine(1-1.5mg/ml,实验组2)。由于一氧化氮在体内易转化为亚硝酸盐和硝酸盐,因此使用亚硝酸钠作为第二个对照组,以区分一氧化氮和亚硝酸盐的潜在影响(对照组2)。所有实验均在室温下渗透压为305±5mOsm的条件下进行,暴露时间长达90分钟。使用倒置显微镜观察细胞,并在IMAGE Pro-Plus程序上记录和分析图像。

结果

暴露于标准浴液或亚硝酸钠的外毛细胞(对照组1和2)在细胞形状或长度上无明显变化。暴露于S-亚硝基-N-乙酰-L-青霉胺和3-吗啉代-synonimine的细胞出现肿胀,平均细胞长度显著缩短(p<0.01)。

结论

本研究表明,暴露于一氧化氮会导致分离的外毛细胞发生不可逆的形态学变化,提示一氧化氮自由基可能参与慢性中耳炎后遗症感音神经性听力损失的发生。

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