miR-182 prevented ototoxic deafness induced by co-administration of kanamycin and furosemide in rats
miR-182 prevented ototoxic deafness induced by co-administration of kanamycin and furosemide in rats
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miR-182可预防卡那霉素和呋塞米联合给药引起的大鼠耳毒性耳聋
DOI：
10.1016/j.neulet.2020.134861
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发表时间：
2020-04-01
影响因子：
2.5
通讯作者：
Zha，Dingjun
中科院分区：
文献类型：
--
作者：
Chen，Jun;Liu，Zhenzhen;Zha，Dingjun
耳毒性药物可引起听觉感觉毛细胞损失和永久性耳聋，然而，对于这种副作用仍然没有有效的治疗或预防策略。最近的一项研究发现microRNA 182（miR-182）在体外保护耳蜗毛细胞免受耳毒性药物诱导的凋亡。然而，miR-182是否能在体内保护药物诱导的肿瘤仍不清楚。在这项研究中，我们通过跨圆窗龛递送miR-182模拟物在Sprague-Dawley大鼠中过表达耳蜗miR-182。大鼠随后接受卡那霉素和速尿腹腔注射，诱导急性耳蜗外毛细胞死亡和永久性耳聋。听觉脑干反应测试显示，miR-182减弱了永久性阈值偏移。与此结果一致，miR-182减少了外毛细胞的损失和静纤毛的缺失。卡那霉素和速尿联合给药后，miR-182处理还增加了外毛细胞中磷酸肌醇-3激酶调节亚基p85α的水平。我们的研究结果表明，miR-182对耳毒性药物诱导的急性听觉感觉毛细胞丢失和永久性耳聋具有强大的保护潜力。
Ototoxic drugs may induce auditory sensory hair cell loss and permanent deafness; however, there is still no effective treatments or prevention strategies for this side effect. A recent study found that microRNA182 (miR-182) protected cochlear hair cells from ototoxic drug-induced apoptosisin vitro. However, it remains unclear whether miR-182 can protect drug-induced deafnessin vivo. In this study, we overexpressed cochlear miR-182 in Sprague-Dawley rats by trans-round window niche delivery of miR-182 mimics. The rats subsequently received intraperitoneal injections of kanamycin and furosemide to induce acute cochlear outer hair cell death and permanent deafness. Auditory brainstem response tests showed that miR-182 attenuated permanent threshold shifts. Consistent with this result, miR-182 reduced the loss of outer hair cells and missing stereocilia. miR-182 treatment also increased the level of phosphoinositide-3 kinase regulatory subunit p85α in the outer hair cells after co-administration of kanamycin and furosemide. Our findings suggest that miR-182 has powerful protective potential against ototoxic drug-induced acute auditory sensory hair cell loss and permanent deafness.