Wang Yanru, Qu Yan, Chen Xuzhen, Zhang Pu, Su Dan, Wang Li, Yang Feifei, Yang Jiangdong
1 Department of Otorhinolaryngology, The 980th Hospital of the Joint Logistics Support Force of the Chinese Peopole's Liberation Army, Shijiazhuang, China.
2 Department of Otorhinolaryngology, The Third Hospital of Hebei Medical University, Shijiazhuang, China.
J Int Med Res. 2019 Aug;47(8):3874-3885. doi: 10.1177/0300060519860679. Epub 2019 Jul 21.
To study the effects of D-methionine in a mouse model of noise-induced hearing loss (NIHL).
We investigated changes in auditory function and microscopic cochlear structure in a mouse model of NIHL, and carried out 4-hydroxynonenal (4-HNE) immunostaining and terminal deoxynucleotidyl transferase dUTP nick-end labeling, and examined expression levels of connexins 26 and 30 by western blot.
The auditory brainstem response threshold was significantly increased by noise exposure. Noise exposure also damaged the inner and particularly the outer hair cells in the cochlear basement membrane, while histochemistry demonstrated only scattered loss of hair cells in the basement membrane in mice treated with D-methionine before or after noise exposure. D-methionine inhibited apoptosis in the cochlear basement membrane, stria vascularis, and spiral ligament. 4-HNE expression in the basement membrane, stria vascularis, and spiral collateral ligament was increased by noise exposure, but this increase was attenuated by D-methionine. Connexin 26 and connexin 30 expression levels were reduced by noise exposure, and this effect was similarly attenuated by D-methionine administered either before or after noise exposure.
D-methionine administered before or after noise exposure could rescue NIHL by protecting cochlear morphology, inhibiting apoptosis, and maintaining connexin 26 and 30 expression.
研究D-蛋氨酸在噪声性听力损失(NIHL)小鼠模型中的作用。
我们在NIHL小鼠模型中研究了听觉功能和耳蜗微观结构的变化,进行了4-羟基壬烯醛(4-HNE)免疫染色和末端脱氧核苷酸转移酶dUTP缺口末端标记,并通过蛋白质印迹法检测了连接蛋白26和30的表达水平。
噪声暴露显著提高了听觉脑干反应阈值。噪声暴露还损害了耳蜗基底膜中的内毛细胞,尤其是外毛细胞,而组织化学显示,在噪声暴露前后用D-蛋氨酸处理的小鼠中,基底膜中仅有散在的毛细胞损失。D-蛋氨酸抑制了耳蜗基底膜、血管纹和螺旋韧带中的细胞凋亡。噪声暴露使基底膜、血管纹和螺旋副韧带中的4-HNE表达增加,但D-蛋氨酸减弱了这种增加。噪声暴露降低了连接蛋白26和连接蛋白30的表达水平,在噪声暴露前后给予D-蛋氨酸同样减弱了这种作用。
在噪声暴露前后给予D-蛋氨酸可通过保护耳蜗形态、抑制细胞凋亡和维持连接蛋白26和30的表达来挽救噪声性听力损失。