低剂量顺铂对小鼠耳蜗内毛细胞形态及otoferlin蛋白的影响-论文.pdf

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1、2014焦临床耳鼻咽喉头颈外科杂志28卷11期JClin0torhinolaryngo1HeadNeckSurg(China)·793·低剂量顺铂对小鼠耳蜗内毛细胞形态及otoferlin蛋白的影响*孙颖蒋晓君陈小宏袁伟[摘要]目的：建立稳定有效的低剂量顺铂损伤听觉模型，探讨顺铂造成听功能损伤的机制。方法：将C57小鼠随机分为7组，分别为正常组，不同剂量、不同时间损伤实验组，每组8只。通过小鼠听性脑干反应(ABR)阈值测量、AgNO。毛细胞形态染色、免疫荧光法、RT—PCR测定基膜底回内毛细胞otoferlin蛋白的表达等方式检测顺铂对耳蜗内毛细胞形态及otoferlin蛋白的影响

2、。结果：在同一时间点，用药4d后，1．5mg／kg和3．0mg／kg实验组较正常组小鼠ABR阈值明显升高，用药7d的各实验组ABR阈值较正常组均明显升高。同一剂量下，0．75mg／kg×7d组较0．75mg／kg×4d组阈值明显增高，其余剂量无明显时间差异。实验组中3．0mg／kg实验组蛋白表达均降低，1．5mg／kg实验组与正常组无差异。3．0mg／kg×7d组内毛细胞形态改变最明显，但在各组均未缺失。结论：低剂量顺铂可造成昕功能损伤，其损伤机制很可能与内毛细胞的损伤及otoferlin蛋白有关。[关键词]顺铂；内毛细胞；听性脑干反应doi：10．13201／j．issn．100

3、1—1781．2014．11．011[中图分类号]R764[文献标志码]AEffectoflowdosageofciplatinontheshapeandotoferlinincochleainnerhaircellsSUNYingJANGXiaojnCHENXiaohongyU_ANWi(DepartmentofOtorhinolaryngo1ogy，SouthwestHospitaloftheThirdMilitaryMedicalUniver—sity，Chongqing，400038，China)Correspondingauthor：YUANWei，E—mail：weiy

4、uan175@sina．cornAbstract0hiective：Toestablishthestableandefficienthearingdamagemodelbyusinglowdosageofcispla—tin，andinvestigatethemechanism．Method：C57miceweredividedinto7groups(everygroup，=8)，thefirstgroupwasthecontrolgroup，theotherswereseparatelyintraperitonea1lyinjectedwithdifferentdosagesof

5、cispla—tinfordifferenttime．Wemeasuredtheauditorybrainstemresponse(ABR)ofthemice。andobtainedthebasalcoiloforganCorti．Weobservedtheshapeofinnerhaircells(IHC)bystainingAgNO3andmarkedotoferlinintheIHCbyimmunofluorescence，successivelyslicedbylaserconfocalmicroscopy．TheRNAfragmentswereamplifiedbyRT—

6、PCR．Result：Aftercisplatinadministrationforfourdays，thethresholdsoftheABRimprovedin1．5mg／kgand3．0mg／kggroup，andcomparedwiththecontrolgroup，theABRthresholdsimprovedineachgroupwithciplatinadministrationforsevendays．Withthesamedosage。theABRthresholdofthe0．75mg／kg×7dgroupwashigherthan0．75mg／kg×4dgr

7、oup．andtherewasnotime—effectrelationshipexistinginothergroupswithdifferentdosage．Theotoferlinwaslessexpressed3．0mg／kggroupsthanthecontrolgroup．However，theoto—ferlinexpressedinthe1．5mg／kggroupswerealmostthesameasthecontrolgroup．Thealtera