Histone deacetylase inhibitor sodium butyrate attenuates gentamicin-induced hearing loss in vivo
Histone deacetylase inhibitor sodium butyrate attenuates gentamicin-induced hearing loss in vivo
复制标题
组蛋白脱乙酰酶抑制剂丁酸钠可减轻庆大霉素引起的体内听力损失
DOI：
10.1016/j.amjoto.2014.11.003
复制
发表时间：
2015-03-01
影响因子：
2.5
通讯作者：
Chen, Fu-quan
中科院分区：
文献类型：
--
作者：
Wang, Jie;Wang, Ye;Chen, Fu-quan
目的：尽管组蛋白去乙酰化酶（HDAC）抑制剂已在体外被证明可预防庆大霉素（GM）诱导的听力损失，但其在体内的保护作用尚未得到证实。在本研究中，目的是探讨一种特异性HDAC抑制剂丁酸钠（NaB）在体内对GM诱导的耳毒性的保护作用。
方法：将40只8周龄的白化豚鼠分为两个实验组。第1组（n = 10）进行双侧耳部手术，分别在右耳和左耳圆窗龛放置浸透NaB（10 μl，100 mg/ml）和生理盐水（10 μl；对照）的海绵（0.3 mm³）。将海绵放置15天以评估所应用浓度的NaB的效果。第2组（n = 30）进行与第1组相同的双侧耳部手术，但在手术后3天，动物连续5天接受肌肉注射GM（200 mg/kg/天）。在最后一次GM注射7天后，检查NaB的保护作用。
结果：在NaB治疗（10 μl，100 mg/ml）15天后，在柯蒂器样本中检测到组蛋白乙酰化增加。在给予GM后，NaB处理的耳朵的听性脑干反应（ABR）阈值偏移和毛细胞损失也减少。此外，GM治疗在体内增加了外毛细胞（OHCs）中HDAC1的表达，而NaB阻断了这一作用。
结论：GM增加OHCs中HDAC1的表达，而NaB能够阻断这一作用。因此，似乎HDAC抑制剂NaB可减轻豚鼠中GM诱导的听力损失。（C）2015爱思唯尔公司。保留所有权利。
Objective: Although histone deacetylase (HDAC) inhibition has been shown to protect against gentamicin (GM)-induced hearing loss in vitro, its protective effect has not been proven in vivo. In the present study, the aim was to investigate the protective effect of sodium butyrate (NaB), a specific HDAC inhibitor, on GM-induced ototoxicity in vivo.Methods: Forty 8-week-old albino guinea pigs were divided into two experimental groups. Group 1 (n = 10) underwent bilateral ear surgery to place sponges (0.3 mm(3)) permeated with NaB (10 mu l, 100 mg/ml) and physiological saline (10 mu l; control) in the right and left round window niches, respectively. The sponges were left in place for 15 days to evaluate the effects of NaB at the applied concentration. Group 2 (n = 30) underwent the same bilateral ear surgery described for Group 1, except three days after surgery, the animals received intramuscular GM injections (200 mg/kg/day) for 5 consecutive days. Seven days after the final GM injection, the protective effects of NaB were examined.Results: After 15 days of NaB treatment (10 mu l, 100 mg/ml), an increase in histone acetylation was detected in Corti organ samples. Auditory brainstem response (ABR) threshold shifts and hair cell loss were also reduced in NaB-treated ears after GM administration. Furthermore, GM treatment increased HDAC1 expression in outer hair cells (OHCs) in vivo, and NaB blocked this action.Conclusion: GM increases HDAC1 expression in OHCs, and NaB is able to block this action. Thus, it appears that the HDAC inhibitor, NaB, attenuates GM-induced hearing loss in guinea pigs. (C) 2015 Elsevier Inc. All rights reserved.