Yang W, Hu B, Guo W, Hu Y, Wang P, Jiang S
Institute of Otorhinolaryngology, Chinese PLA General Hospital, Beijing 100853, China.
Zhonghua Er Bi Yan Hou Ke Za Zhi. 2001 Oct;36(5):342-5.
To investigate if glial cell line-derived neurotrophic factor (GDNF) combined with neurotrophin-3 (NT-3) provides synergetic protection in filamentous actin (F-actin) on hair cell (HC) from acoustic trauma.
Guinea pigs were exposed to 4 kHz narrow band noise at 115 dB SPL for 4 h. Test group (n = 12) with a mixture of GDNF (100 ng/ml) and NT-3(2.5 micrograms/ml) or control group (n = 9) with artificial perilymph (AP) was delivered to the scala tympani via a mini-osmotic pump (0.5 microliter/h) for a total of 14 days. Auditory function was assessed by measuring thresholds of auditory brainstem responses (ABRs) elicited by clicks prior to surgery, 3 days after surgery (1 day before noise exposure) and 10 days following noise exposure (before animals were sacrificed), respectively. F-actin, labeled by rhodamine-phalloidin, was examined in the guinea pig cochlea using fluorescence microscopy for quantitative assessment of hair cell damage.
There was a statistically significant increase the survival of out hair cell(P < 0.001, P < 0.01) and inner hair cell(P < 0.01, P < 0.01) and decrease in ABR threshold (P < 0.05, P < 0.01) in both the GDNF and NT-3 treated and untreated ear of animals.
Our findings indicate that GDNF combined with NT-3 may effectively protect the inner ear from noise--induced hearing loss.
研究胶质细胞源性神经营养因子(GDNF)与神经营养因子-3(NT-3)联合应用是否能对声损伤豚鼠毛细胞的丝状肌动蛋白(F-肌动蛋白)提供协同保护作用。
将豚鼠暴露于115 dB SPL的4 kHz窄带噪声中4小时。通过微型渗透泵(0.5微升/小时)将含有GDNF(100纳克/毫升)和NT-3(2.5微克/毫升)混合物的试验组(n = 12)或含有人工外淋巴(AP)的对照组(n = 9)注入鼓阶,共14天。分别在手术前、手术后3天(噪声暴露前1天)和噪声暴露后10天(动物处死前)通过测量点击诱发的听觉脑干反应(ABR)阈值来评估听觉功能。用罗丹明-鬼笔环肽标记F-肌动蛋白,通过荧光显微镜检查豚鼠耳蜗,以定量评估毛细胞损伤。
在接受GDNF和NT-3治疗及未治疗的动物耳中,外毛细胞(P < 0.001,P < 0.01)和内毛细胞(P < 0.01,P < 0.01)的存活率均有统计学显著提高,ABR阈值降低(P < 0.05,P < 0.01)。
我们的研究结果表明,GDNF与NT-3联合应用可能有效保护内耳免受噪声诱导的听力损失。