硫普罗宁对顺铂所致耳毒性的保护作用  

Protective Role of Tiopronin against Ototoxicity Caused by Cisplatin

作　　者：刘慧茹[1] 陈学明[1] 王士礼[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院耳鼻咽喉科,上海200023

出　　处：《听力学及言语疾病杂志》2007年第4期310-312,315,I0003,共5页Journal of Audiology and Speech Pathology

摘　　要：目的探讨硫普罗宁对顺铂耳毒性的保护作用。方法将48只豚鼠随机等分为四组,每组12只:生理盐水对照组:生理盐水腹腔注射2ml/d共7天;硫普罗宁组:腹腔注射硫普罗宁0.3g·kg-1·d-1共7天;顺铂组:腹腔注射顺铂4mg·kg-1·d-1共4天;顺铂加硫普罗宁组:先腹腔注射硫普罗宁0.3g·kg-1·d-13天,从第4天起先腹腔注射硫普罗宁0.3g·kg-1·d-1,再腹腔注射顺铂4mg·kg-1·d-1共4天。动物用药前后行听性脑干反应检查。每组半数动物做耳蜗基底膜铺片硝酸银染色,在光镜下观察毛细胞形态,半数动物取耳蜗组织匀浆测局部丙二醛(malonaldehyde,MDA)和超氧化物歧化酶(superoxide dismutase,SOD)的含量。结果顺铂应用后可使(auditory brainstem response,ABR)反应阈上升,波I潜伏期延长,耳蜗组织匀浆内MDA含量增多,SOD活性下降,与生理盐水对照组相比差异具有显著统计学意义(P<0.01)。硫普罗宁可改善顺铂的耳毒性,使ABR反应阈下降,波I潜伏期缩短,局部MDA含量减少,SOD活性提高,与顺铂组相比差异具有显著统计学意义(P<0.05)。光镜下见应用顺铂后外毛细胞明显损伤,而硫普罗宁可减轻上述损伤。结论硫普罗宁可能通过抗自由基原理来改善顺铂的耳毒性。Objective The propose of this study was to evaluate cisplatin - induced ototoxicity and the protective effects of tiopronin. Methods Forty eight adult guinea pigs were divided into four groups. Group A received saline as controls. Group B receiving tiopronin was used as another controls. Group C received cisplatin （4 mg/kg） injections for 4 consecutive days, and group D firstly received tiopronin （300 mg/kg） for 3 consecutive days, then received both cisplatin（4 mg/kg） and tiopronin （300 mg/kg） for4 consecutive days . Both ears of all the animals were tested with auditory brainstem response （ABR） before and on the 8th day of the corresponding treatment. All the animals were sacrificed after the final recording session, and half cochleas in each group were collected for the surface preparation of basilar membrane and light microscopy analysis. The other half cochleas were collected for analysis of MDA and SOD in the tissue homogeuate. Results The ABR threshold was significantly increased and the latency of wave I was significantly prolonged in cisplatin group compared to controls. Significant increase of MDA and decrease of SOD were also noted in the tissue homogeuate. When tiopronin was added, the auditory threshold was significantly decreased and the latency of wave I was significantly reduced compared to the cisplatin group. The MDA was significantly decreased while the activity of SOD significantly increased. The outer hair cells in the cochlear were cearly damaged after cisplatin was applied. The damage could be effectively reduced by tiopronin. Conclusion Tiopronin seems to be an effective drug in protecting against cisplation induced ototoxicity and this may be related to anti - free radicals.

关 键 词：顺铂 硫普罗宁 自由基 豚鼠 

分 类 号：R764.5[医药卫生—耳鼻咽喉科]