de Groot J C, Hamers F P, Gispen W H, Smoorenburg G F
Department of Otorhinolaryngology, University Hospital Utrecht, The Netherlands.
Hear Res. 1997 Apr;106(1-2):9-19. doi: 10.1016/s0378-5955(96)00213-4.
In this study the effect of the neurotrophic ACTH(4-9) analogue, ORG 2766, on cisplatin cochleotoxicity was investigated with both light- and transmission electron microscopy. Guinea pigs were treated with either cisplatin+ORG 2766 (n = 11) or cisplatin + physiological saline (n = 9). All animals treated with cisplatin + physiological saline showed complete loss of outer hair cells (OHC) and degeneration of the organ of Corti in the basal cochlear turns, while partial OHC loss was found in the middle and apical turns. The inner hair cells (IHC) and other cochlear tissues were not affected. Eight animals from the group treated with cisplatin + ORG 2766 demonstrated similar pathological changes, but to a lesser degree, especially in the middle turns. The three remaining animals demonstrated no cochlear alterations at all, light-microscopically, and only minor subcellular changes in the OHCs at the ultrastructural level. Electrophysiologically, these three animals showed normals compound action potential (CAP) amplitudes at stimulus frequencies from 0.5 to 16 kHz and normal cochlear microphonics (CM) in the frequency range from 0.5 to 8 kHz. The other animals treated with cisplatin + ORG 2766 showed a severe loss in their CAPs and CM, except for one showing intermediate loss. All animals from the group treated with cisplatin alone showed a severe loss in their CAPs and CM. Endolymphatic hydrops was present in all animals from the cisplatin- and the cisplatin + ORG 2766-treated groups. These data indicate that daily, concomitant administration of ORG 2766 may reduce OHC loss and subsequent degeneration of the organ of Corti in cisplatin-treated guinea pig cochleas.
在本研究中，运用光学显微镜和透射电子显微镜研究了神经营养性促肾上腺皮质激素（4-9）类似物ORG 2766对顺铂耳毒性的影响。豚鼠分别接受顺铂+ORG 2766治疗（n = 11）或顺铂+生理盐水治疗（n = 9）。所有接受顺铂+生理盐水治疗的动物在耳蜗基部螺旋中均出现外毛细胞（OHC）完全丧失以及柯蒂氏器退化，而在中部和顶部螺旋中发现部分OHC丧失。内毛细胞（IHC）和其他耳蜗组织未受影响。顺铂+ORG 2766治疗组的8只动物表现出类似的病理变化，但程度较轻，尤其是在中部螺旋。其余3只动物在光学显微镜下未显示耳蜗改变，仅在超微结构水平上OHC有轻微亚细胞变化。电生理学上，这3只动物在0.5至16 kHz的刺激频率下复合动作电位（CAP）振幅正常，在0.5至8 kHz频率范围内耳蜗微音电位（CM）正常。其他接受顺铂+ORG 2766治疗的动物除1只表现为中度丧失外，其CAP和CM均严重丧失。所有单独接受顺铂治疗的动物其CAP和CM均严重丧失。顺铂治疗组和顺铂+ORG 2766治疗组的所有动物均存在内淋巴积水。这些数据表明，每日同时给予ORG 2766可能会减少顺铂治疗的豚鼠耳蜗中OHC丧失及随后的柯蒂氏器退化。
