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目的:探讨腺伴随病毒(AAV)介导活性依赖性神经营养因子-9(ADNF-9)基因转染对卡那霉素致豚鼠耳毒性的拮抗作用。方法:选用80只白色红目豚鼠,听功能正常,随机分为四组,每组20只,A组(ADNF-9保护组):左耳经圆窗注入ADNF-9后肌注卡那霉素;B组(空载体组):左耳经圆窗注入AAV,后肌注卡那霉素;C组(人工淋巴液组):左耳经圆窗注入人工淋巴液后肌注卡那霉素;D组(空白对照组):仅肌注卡那霉素。卡那霉素均经大腿内侧注射400 mg/(kg·d),共给药6d;停药后6、14d各组均行听性脑干反应(ABR)检测,停药14d后各组处死动物,行耳蜗石蜡病理切片及耳蜗基底膜铺片观察各组豚鼠耳蜗基底膜毛细胞形态学。结果:实验前所有豚鼠的听功能均正常;停药后6、14d的ABR阈值A组为(32.54±5.28)dB和(33.52±2.26)dB;B组为(77.56±4.18)dB和(78.00±5.48)dB;C组为(75.24±6.72)dB和(77.25±4.65)dB;D组为(78.00±3.32)dB和(78.25±3.26)dB。A组停药后6、14d与B组、C组及D组比较有统计学差异(P<0.05)。耳蜗病理切片及基底膜铺片均提示:A组耳蜗螺旋器细胞损害较轻,基底膜板基本完整;其余三组,耳蜗螺旋器毛细胞损害严重,基底膜有不同程度的损害。结论:ADNF-9基因转染可以有效拮抗氨基糖苷类所致豚鼠耳毒性。
Objective: To investigate the antagonism of adeno-associated virus (AAV) -mediated activity-dependent neurotrophic factor-9 (ADNF-9) gene transfection on ototoxicity induced by kanamycin in guinea pigs. Methods: Eighty white-red guinea pigs were selected and their hearing function was normal. They were randomly divided into four groups with 20 rats in each group. Group A (ADNF-9 protection group): After intramuscular injection of ADNF- Group B (empty vector group): AAV was injected into the left ear through the round window and kanamycin was intramuscularly injected; Group C (artificial lymphatic fluid group): the left ear was injected intramuscularly with kanamycin D group (blank control group): only intramuscular injection of kanamycin. Kanamycin were injected 400 mg / (kg · d) into the thigh for 6 days. All rats in each group were subjected to auditory brainstem response (ABR) at 6 and 14 days after drug withdrawal. All rats were sacrificed 14 days after drug withdrawal Animals, cochlear wax pathological sections and cochlear basement membrane were observed in each group of guinea pig cochlear basement membrane hair cell morphology. Results: The hearing function of all guinea pigs was normal before the experiment. The threshold of ABR at 6 and 14 days after drug withdrawal was (32.54 ± 5.28) dB and (33.52 ± 2.26) dB in group A, and (77.56 ± 4.18) dB and ± 5.48) dB; group C was (75.24 ± 6.72) dB and (77.25 ± 4.65) dB; group D was (78.00 ± 3.32) dB and (78.25 ± 3.26) dB. There was a significant difference (P <0.05) between group A and group B, group C and group D on days 6 and 14 after discontinuation. Cochlear biopsy and basilar membrane patch suggest that: A group of cochlear spiral cells less damage, basilar membrane basic integrity; the other three groups, severe damage to the cochlear spiral cells, basilar membrane damage in varying degrees. Conclusion: ADNF-9 gene transfection can effectively antagonize aminoglycoside induced guinea pig ototoxicity.