Comparative analysis of combination kanamycin-furosemide versus kanamycin alone in the mouse cochlea.
Comparative analysis of combination kanamycin-furosemide versus kanamycin alone in the mouse cochlea.
复制标题
小鼠耳蜗中单独的卡纳米霉素 - 氟霉素与卡那霉素的比较分析。
DOI：
10.1016/j.heares.2010.10.011
复制
发表时间：
2011-02
期刊：
影响因子：
2.8
通讯作者：
Sato E
中科院分区：
文献类型：
--
作者：
Hirose K;Sato E
已知氨基糖苷类和袢利尿剂的组合在耳毒性损伤中具有协同作用。由于与其他哺乳动物相比，小鼠毛细胞对耳毒性的抵抗力相对较高，因此研究人员转向联合疗法，在小鼠内耳中产生耳毒性损伤。在本文中，我们对卡那霉素与卡那霉素/呋塞米联合用药后的听力阈值、毛细胞损伤和单核细胞向小鼠耳蜗的迁移进行了系统比较，并探讨了袢利尿剂存在下氨基糖苷类耳毒性中毛细胞损失增强的病理生理学。与单独使用卡那霉素相比，卡那霉素-呋塞米组合不仅导致高频阈值升高，而且导致所有频率的阈值升高，并且外毛细胞损失更广泛。卡那霉素-呋塞米暴露小鼠的血管纹严重萎缩，螺旋缘星状细胞缺失，而单独接受卡那霉素的小鼠则没有观察到这些变化。单核细胞和巨噬细胞被大量募集到这些小鼠的螺旋韧带和螺旋神经节中。与单独给予卡那霉素的小鼠相比，联合治疗导致巨噬细胞总数更多，并且顶部存在更多的巨噬细胞。卡那霉素-呋塞米组合提供了一种有效的方法来解决在大多数小鼠品系中观察到的对耳毒性的相对抵抗力。随着小鼠在听力损失研究中变得越来越常见，并且联合疗法越来越受欢迎，认识到氨基糖苷环利尿剂联合疗法的总体效果对于解释随后的干预措施至关重要。
Combinations of aminoglycosides and loop diuretics have been known to have a synergistic effect in ototoxic injury. Because murine hair cells are relatively resistant to ototoxicity compared to those of other mammals, investigators have turned to combination therapies to create ototoxic lesions in the mouse inner ear. In this paper, we perform a systematic comparison of hearing thresholds, hair cell damage and monocyte migration into the mouse cochlea after kanamycin versus combined kanamycin/furosemide and explore the pathophysiology of enhanced hair cell loss in aminoglycoside ototoxicity in the presence of loop diuretic. Combined kanamycin-furosemide resulted in elevation of threshold not only in the high frequencies, but across all frequencies with more extensive loss of outer hair cells when compared to kanamycin alone. The stria vascularis was severely atrophied and stellate cells in the spiral limbus were missing in kanamycin-furosemide exposed mice while these changes were not observed in mice receiving kanamycin alone. Monocytes and macrophages were recruited in large numbers to the spiral ligament and spiral ganglion in these mice. Combination therapy resulted in a greater number of macrophages in total, and many more macrophages were present further apically when compared to mice given kanamycin alone. Combined kanamycin-furosemide provides an effective method of addressing the relative resistance to ototoxicity that is observed in most mouse strains. As the mouse becomes increasingly more common in studies of hearing loss, and combination therapies gain popularity, recognition of the overall effects of combined aminoglycoside-loop diuretic therapy will be critical to interpretation of the interventions that follow.