顺铂对耳蜗血管纹毒性作用的研究  

Cisplatin Toxicity on Stria Vascularis

作　　者：李轶[1] 刘会占 何志洲 LI Yi;LIU Huizhan;HE Zhizhou(Department of Otorhinolaryngology-Head and Neck Surgery,Beijing Tongren Hospital,Ministry of Education of China,Key Laboratory of Otorhinolaryngology-Head and Neck Surgery,Capital Medical University,Beijing,100730;Department of Biomedical Sciences,Creighton University School of Medicine,Omaha,Nebraska 68178,USA)

机构地区：[1]首都医科大学附属北京同仁医院院耳鼻咽喉头颈外科耳鼻咽喉头颈科学教育部重点实验室首都医科大学,北京100730 [2]Department of Biomedical Sciences, Creighton University School of Medicine

出　　处：《中华耳科学杂志》2019年第1期82-87,共6页Chinese Journal of Otology

基　　金：国家自然科学基金(81600798)~~

摘　　要：目的探讨顺铂对内耳血管纹的毒性机制。方法使用在体小鼠模型,用记录内淋巴电位的方法,研究使用顺铂是否可以迅速影响内淋巴电位的幅度。用离体培养的小鼠的血管纹中间细胞,记录中间细胞的膜电位,观察顺铂是否能够影响中间细胞胞膜上离子泵的转运能力和离子通道的通透性。结果在实验动物中注射顺铂后并不能改变其内淋巴电位的幅度。在培养的中间细胞上观察到,灌流顺铂对细胞静息膜电位没有影响。结论使用顺铂一个疗程后出现的内淋巴电位降低,并不是通过对血管纹上离子通道或离子泵的影响引起的,顺铂对血管纹的功能不能造成急性损伤。Objective To determine mechanisms of cisplatin toxicity to stria vascularis in adult mice.A recent study has showed that cisplatin retains in the stria vascularis for a long period of time and is detrimental to stria function.Our goal is to determine whether cisplatin toxicity to stria is mediated by blocking Na+/K+-ATPase,Na+/K+/2Cl?cotransporter and K+channels in the cell membrane of stria cells.Methods Endocochlear potential was measured using the sharp electrode technique when cisplatin was administrated to the tail vein in adult mice.Whole-cell patch-clamp technique was used to measure membrane potential from cultured melanocytes prepared from neonatal mice.Results We showed that there was no significant reduction of endocochlear potential within 30 minutes after cisplatin was administrated to the circulation.In contrast,significant reduction of endocochlear potential was observed within seconds after hypoxia.Cisplatin administration also did not lead to change of the resting membrane potential of cultured melanocytes.Conclusion While cisplatin is detrimental to stria function,it appears that its toxicity is not mediated by blocking Na+/K+-ATPase,Na+/K+/2Cl?cotransporter and K+channels in the cell membrane of the three types of cells in the stria.It is likely that cisplatin may damage stria morphology and function through mechanisms of oxidative stress and DNA damage,similar to those that cause loss of cochlear hair cells.

关 键 词：顺铂 血管纹 内淋巴电位 

分 类 号：R764[医药卫生—耳鼻咽喉科]