神经营养因子对噪声引起豚鼠耳蜗外毛细胞损伤的防护作用

目的 定量观察胶质细胞源性神经营养因子(glial cell ine-derived neurotrophic factor,GDNF)和神经营养-3(neurotrophin-3,NT-3)对噪声引起豚鼠耳蜗外毛细胞损伤的防护作用。方法 将微渗透压泵埋置于豚鼠背部,经固定于耳蜗底回鼓阶内的改良微导管将GDNF(100ng/ml)和NT-3(2.5μg/ml)的混合液缓慢注入12只豚鼠左侧内耳,以左侧内耳灌注人工外淋巴液的9只豚鼠为对照,检测噪声暴露后豚鼠听功能和耳蜗外毛细胞形态、数量的变化。结果 噪声暴露10天后,实验组手术耳和非手术耳的脑干诱发电反应阈值低于对照组(P<0.05,p<0.01)。毛细胞表皮板和纤毛肌动蛋白荧光染色计数发现,实验组手术耳和非手术耳的外毛细胞缺失率低于对照组(p<0.001,p<0.01)。毛细胞核荧光染色计数发现,实验组手术耳和非手术耳的外毛细胞核肿胀率低于对照组(p<0.01,p<0.01)。结论 GDNF和NT-3对噪声引起豚鼠耳蜗外毛细胞损伤具有较好的防护作用。

Neurotrophins decrease degeneration of out hair cells of the guinea pig after noise trauma

Objective To investigate whether glial cell line - derived neurotrophic factor (GDNF) combined with neurotrophin- 3 (NT- 3) provides the synergetic protection on hair cells (HC) from acoustic trauma. Methods Guinea pigs were ex-posed to a 4 kHz narrow band noise at 115 dB SPL for 4 hrs. The left cochlea of the animals was infused with aaificial perilymph (AP) containing (the test group) or without containing (the control group) a mixture of GDNF ( 100 ng/ml) and NT- 3(2.5μg/ml) via a mini - osmotic pump connected to the scala tympani. The infusion began at 4 days before the noise exposure and continued for 10 days after the noise exposure. Hearing function was assessed by measuring the thresholds of auditory brainstem responses (ABRs) elicited by clicks, before and 3 days after the osmotic pump implantation, and repeated 10 days after the noise exposure ( 14 days after the pump implantation). The numbers of damaged OHCs were quantitatively assessed by staining with rhodamine - phalloidin for F- actin in the cuticular plates and with Hoechst 33342 for HC nuclei. Results There was a statistically significant increase in the number of survived out hair cell (OHC) (p ＜ 0. 001, p ＜ 0.01 ) and a decrease in ABR threshold shifts (p ＜ 0.05, p ＜ 0.01 ) in both treated (left) and untreated ( right ) ears of animals received GDNF and NT- 3. Conclusion These findings indicate that GDNF combined with NT- 3 can effectively protects OHCs from noise - induced damage.