Calpain immunoreactivity and morphological damage in chinchilla inner ears after carboplatin
Calpain immunoreactivity and morphological damage in chinchilla inner ears after carboplatin
复制标题
DOI：
10.1007/s101620020004
复制
发表时间：
2002-03-01
影响因子：
2.4
通讯作者：
Salvi, RJ
中科院分区：
文献类型：
--
作者：
Ding, DL;McFadden, SL;Salvi, RJ
卡铂在龙猫内耳中产生一种不寻常的损伤模式，其特征是耳部I型传入纤维的破坏和前庭末端器官和耳蜗内毛细胞（IHCs）的I型毛细胞的优先损失。在本研究中，我们研究了钙蛋白酶家族在卡铂耳毒性中的潜在作用。龙猫接受卡铂（100 mg/kg IP）治疗，12、24、48、72 h后处死，进行形态学评价或免疫细胞化学。神经纤维和髓鞘是钙蛋白酶免疫反应性（IR）升高和形态学损伤的起始部位。12 h时，螺旋神经节神经纤维及其髓鞘内可见颗粒状免疫反应小点。在穿孔束中，密集的反应产物存在于神经纤维周围髓鞘的大空泡中。24h时，缰核内神经纤维和髓鞘被破坏，螺旋神经节内钙蛋白酶IR增加，形态学损伤。72h时，神经纤维和髓磷脂被完全破坏。在卡铂治疗后的任何时间，钙蛋白酶IR都不是ihc、I型前庭毛细胞或神经节细胞的显著特征。结果显示calpain IR与卡铂诱导的轴突和髓鞘变性之间存在相关性。我们认为calpain诱导的轴索病和髓鞘病是卡铂耳毒性的主要特征。
Carboplatin produces an unusual pattern of damage in the chinchilla inner ear, characterized by earls destruction of type I afferent fibers and preferential loss of type I hair cells in the vestibular end organs and inner hair cells (IHCs) in the cochlea. In the present study, we investigated a potential role of calpains, a family of calcium-activated proteases, in carboplatin ototoxicity. Chinchillas received carboplatin (100 mg/kg IP) and were sacrificed 12, 24, 48, or 72 h later for morphological evaluation or immunocytochemistry. Nerve fibers and myelin were the initial sites of increased calpain immunoreactivity (IR) and morphological damage. At 12 h, granular immunoreactive puncta were present within nerve fibers and their myelin sheaths in the spiral ganglion. In the habenula perforata, dense reaction product was present in large vacuoles in the myelin surrounding the nerve fibers. At 24 h, nerve fibers and myelin were destroyed in the habenula, and those in the spiral ganglion showed increased calpain IR and morphological damage. At 72 h, nerve fibers and myelin were completely destroyed. Calpain IR was not a prominent feature of IHCs, type I vestibular hair cells, or ganglion cells at any time after carboplatin. The results show a correlation between calpain IR and carboplatin-induced axon and myelin degeneration. We propose that calpain-induced axonopathy and myelinopathy are primary features of carboplatin ototoxicity in chinchilla.