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顺铂对斑马鱼(Danio rerio)幼虫内耳和侧线系统的超微结构影响。

Ultrastructural effects of cisplatin on the inner ear and lateral line system of zebrafish (Danio rerio) larvae.

机构信息

Department of Biology and Evolution, University of Ferrara, Ferrara, 44121, Italy.

出版信息

J Appl Toxicol. 2012 Apr;32(4):293-9. doi: 10.1002/jat.1691. Epub 2011 May 18.

DOI:10.1002/jat.1691
PMID:21590781
Abstract

Zebrafish, Danio rerio, has been a prominent model vertebrate for the study of chemical toxicity and human disease. Zebrafish hair cells (HCs) show significant structural, functional and molecular similarities to the mammalian inner ear HCs. We examined the effects of cisplatin, an anti-cancer drug, on HCs of the inner ear and on HCs and support cells (SCs) of neuromasts in zebrafish using transmission and scanning electron microscopy. Forty-five zebrafish larvae, 12 days post-fertilization, were assessed: 15 unexposed controls, 15 exposed to 10 µM cisplatin solution, and 15 exposed to 50 µM cisplatin solution. Hair cells in the cristae and maculae of the inner ear and of neuromasts were extremely sensitive to cisplatin. The drug was associated with vacuolization and the presence of myelinoid bodies in HC cytoplasm and with a condensation of the nuclear chromatin. The predominant pattern of injury was widespread degeneration of mitochondria, which appeared swollen and less electron-dense with disorganized or reduced cristae. Severity of damage seemed to be concentration-dependent, and the inner ear suffered more damage than the lateral line. Alterations similar to those in HCs were also observed in SCs of the neuromasts. Scanning electron microscopy showed loss of kinocilia in neuromasts of fish exposed to the higher concentration of cisplatin.

摘要

斑马鱼(Danio rerio)是研究化学毒性和人类疾病的重要模式脊椎动物。斑马鱼毛细胞(HCs)在结构、功能和分子水平上与哺乳动物内耳 HCs 具有显著的相似性。我们使用透射和扫描电子显微镜检查了顺铂(一种抗癌药物)对内耳 HCs 以及对斑马鱼的感觉上皮毛细胞(SCs)和感觉上皮支持细胞(SCs)的影响。评估了 45 条受精后 12 天的斑马鱼幼虫:15 个未暴露对照组,15 个暴露于 10µM 顺铂溶液组,15 个暴露于 50µM 顺铂溶液组。内耳嵴帽和感觉上皮毛细胞和感觉上皮支持细胞对顺铂极为敏感。该药物与空泡化和 HC 细胞质中髓鞘样体的存在以及核染色质的凝聚有关。主要的损伤模式是广泛的线粒体变性,线粒体肿胀,电子密度降低,嵴排列紊乱或减少。损伤的严重程度似乎与浓度有关,内耳比侧线受到的损伤更严重。感觉上皮支持细胞也观察到与 HCs 相似的变化。扫描电子显微镜显示,暴露于较高浓度顺铂的鱼的感觉上皮毛细胞中的动纤毛丧失。

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