神经营养因子受体在顺铂中毒大鼠耳蜗螺旋神经节中的表达

目的 探讨神经营养因子受体TrkB、TrkC和p75在顺铂中毒大鼠螺旋神经节中的表达及意义.方法 成年Wistar大鼠50只,随机分为对照组(生理盐水5 ml/kg,1次/d,腹腔注射,连续5 d),用药1 d组(顺铂5 mg/kg,腹腔注射),用药3 d组(顺铂5 mg/kg,1次/d,腹腔注射,连续3 d),用药5 d组A(顺铂5 mg/kg,1次/d,腹腔注射,连续5 d,第6天处死),用药5 d组B(顺铂5 mg/kg,1次/d,腹腔注射,连续5 d,第12天处死),每组10只,建立在体顺铂耳毒性模型.通过反转录一聚合酶链反应(RT-PCR)分别检测耳蜗中TrkB、TrkC及p75的mRNA表达最,通过免疫组织化学染色测定TrkB、TrkC及p75蛋白在螺旋神经节巾的表达.结果 成功建立顺铂耳毒性大鼠模型,随着给约时间的延长,TrkB、TrkC和p75在螺旋神经节中的表达呈动态变化.TrkB的mRNA和蛋白表达(x±s,下同)在用药1 d及3 d组分别达到0.76±0.06、88.78±4.28及0.82±0.09、91.64±4.06,与对照组及其他用药组比较差异具有统计学意义(P值均＜0.05);TrkC的mRNA和蛋白表达在用药1 d组达到0.80±0.06和89.66±2.76,与对照组及其他用药纽比较差异具有统计学意义(P值均＜0.05);p75的mRNA和蛋白在对照组和各用药组的表达分别为0.64±0.04、55.16±3.10、0.77±0.04、78.46±3.86、1.01±0.09、105.02±6.61、1.18±0.09、111.10±6.08、0.51±0.04、42.74±±5.20,各用药组与对照组比较差异具有统计学意义(P值均＜0.05).结论 TrkB、TrkC在给药后早期有一过性表达增强,后期表达下降同时听力损失明显,p75在给药后表达逐渐增强.TrkB、TrkC可能参与顺铂中毒性螺旋神经节损伤后的修复过程;p75可能参与顺铂对螺旋神经节细胞的毒性作用,介导神经元凋亡.     

HO-1在顺铂诱导豚鼠螺旋神经元损伤中的作用

目的检测血红素加氧酶-1在豚鼠耳蜗螺旋神经节顺铂损伤后的表达变化。方法通过免疫组织化学及Western Blot技术,观察耳蜗螺旋神经元损伤后HO-1在不同组间的表达变化。将32只健康豚鼠随机分为4组,每组8只。A组对照组:按体重以0.9%生理盐水12ml/kg腹腔注射,早晚各一次,持续3天。B组顺铂组:按体重12mg/kg顺铂腹腔注射(IP),早晚各一次,持续3天。C组阿魏酸(FA)+顺铂组:先150mg/kg FA腹腔注射预处理1h,再以12mg/kg顺铂IP,早晚各一次,持续三天。D组FA+锌原卟啉Ⅸ(ZnppⅨ)+顺铂组:同时给予150mg/kg FA+ZnppⅨ15umol/kg IP预处理1h,再以12mg/kg顺铂IP,早晚各一次,持续三天。采用免疫组织化学及Wstern Blot技术检测不同组间螺旋神经元HO-1蛋白表达变化。结果在不同的分组中,HO-1在耳蜗螺旋神经节中表达量不同。空白组中,螺旋神经节组织存在微弱的HO-1表达,其蛋白表达量为0.48±0.07;A组蛋白表达量为0.81±0.07,B组蛋白表达量为0.9±0.05,C组蛋白表达量为0.61±0.07。4个组两两间差异均有统计学意义(p<0.0001)。结论 HO-1在C组中表达量最多,B组次之,D组最少,表明HO-1可能参与顺铂损伤螺旋神经元后的修复过程。     

顺铂对耳蜗螺旋神经节细胞毒性作用及机制

目的通过透射电镜及免疫组化法观察顺铂对耳蜗螺旋神经节细胞的毒性作用。方法16只豚鼠随机均分为2组。顺铂组连续5天腹腔注射顺铂2mg/kg/d;对照组连续5天腹腔注射生理盐水2mg/kg/d;用药前后测试听力,处死动物后制作耳蜗标本,透射电镜观察及免疫组化法测定诱导型一氧化氮合酶(induciblenitricoxidesynthase,iNOS)的表达。结果ABR:顺铂组听力下降明显,阈值显著升高(P<0.01)。透射电镜观察:顺铂组螺旋神经节细胞的细胞器损伤严重,核变形,线粒体肿胀,大量空泡样变,粗面内质网增多,有髓神经纤维的髓鞘增厚;对照组螺旋神经节细胞核无变形,核仁基本居中,线粒体结构正常。免疫组织化学显示:顺铂组螺旋神经节有iNOS阳性反应显色,灰度值降低,iNOS活性升高,与对照组比较,有显著性差异(P<0.01)。结论顺铂可致耳蜗螺旋神经节细胞损伤并呈iNOS阳性表达,导致听力下降。     

连翘酯苷对顺铂耳毒性防护作用的实验研究

目的观察连翘酯苷对顺铂耳毒性的防护作用并探讨其机制。方法将42只听力正常豚鼠随机分为空白组(10只):腹腔注射生理盐水8.0 ml·kg-1·d-1,连续8天;顺铂组(16只):腹腔注射顺铂2.0 mg·kg-1·d-1,连续8天;拮抗组(16只):前2天腹腔注射连翘酯苷25.0 mg·kg-1·d-1,第3天起腹腔注射连翘酯苷后30 min,再腹腔注射顺铂2.0 mg·kg-1·d-1,连续8天。每组豚鼠首次用药前及末次用药后第二天均行ABR检测,末次检测完毕后,心脏穿刺采血检测血清总超氧化物歧化酶(total superoxide disumutase,T-SOD)活性和丙二醛(malondialdehyde,MDA)含量,最后断头处死并取耳蜗,行硝酸银染色全耳蜗铺片、耳蜗组织切片和扫描电镜观察。结果空白组、顺铂组、拮抗组用药后ABR阈值分别为7.57±4.59、41.65±6.56、30.63±5.02 dB nHL;血清T-SOD活性分别为186.18±23.46、82.61±36.12、123.53±30.76 U/ml;MDA含量分别为4.14±0.79、10.69±1.21、7.85±0.97 nmol/ml。拮抗组ABR阈值低于顺铂组(P<0.05),顺铂组血清中T-SOD活性最低,而MDA含量最高,差异有统计学意义(P<0.5)。顺铂组耳蜗外毛细胞缺失明显,平均缺失率为53.42%,毛细胞结构紊乱,血管纹紊乱、螺旋神经节细胞数减少,而拮抗组这些损害明显减轻。结论连翘酯苷在一定程度上可以防护顺铂所致的耳蜗损伤,机制可能与其清除耳蜗组织氧自由基、减少氧化应激反应有关。     

顺铂作用下沙鼠耳蜗螺旋神经节神经元和Corti器细胞的凋亡

目的　探讨顺铂是否可引起沙鼠耳蜗螺旋神经节 (spiralganglion ,SG)神经元和Corti器细胞的凋亡。方法　对沙鼠进行顺铂连续腹腔注射 ,每日 4mg kg体重 ,分别于健康对照组及给药 4、5、6、7d各处死沙鼠 12只 ,取左侧耳蜗 ,每组动物取 10只耳蜗做平行蜗轴的石蜡切片 ,另 2只耳蜗做底回蜗轴及基底膜超薄切片。通过末端脱氧核苷酸转移酶介导的dUTP缺口末端标记技术 (terminaldeoxynucleotidyltransferase mediateddUTPnickendlabelingmethod ,TUNEL)及透射电镜检测连续用药不同时间后底回SG及Corti器的细胞凋亡情况。结果　连续应用顺铂 5～ 7d ,在透射电镜下可以观察到底回SG神经元及外毛细胞中出现凋亡特征性病理改变 ,TUNEL标记的石蜡切片中可见给药 5d后SG和Corti器出现的阳性细胞明显高于健康对照组 ,给药 6～ 7d阳性细胞进一步增加。结论　细胞凋亡是顺铂损伤沙鼠SG神经元和Corti器细胞的重要方式     

连翘酯苷对顺铂作用后豚鼠耳蜗c-jun表达的影响

目的：研究连翘酯苷对顺铂作用后豚鼠耳蜗c—jun表达的影响。方法：将30只豚鼠随机分为对照组（10只）,顺铂组（10只）和连翘酯苷组（10只）。腹腔注射顺铂溶液（8mg／kg）,1次／d,连续7d,建立顺铂耳毒性模型;连翘酯苷组在每次注射顺铂溶液30rnin前腹腔注射连翘酯苷25．0mg／kg／d,连续7d;对照组以生理盐水代替顺铂溶液注射,连续7d。实验动物被处死前,检测其DPOAE幅值变化;采用蛋白质印迹杂交（Western Blotting）检测各组豚鼠耳蜗c—jun蛋白的表达,逆转录聚合酶链反应检测各组豚鼠耳蜗c—jun基因mRNA的表达。结果：顺铂组DPOAE幅值明显低于对照组（P〈0．01）;相比于顺铂组,连翘酯苷组DPOAE幅值明显升高（P〈0．05）。顺铂组豚鼠耳蜗c—jun蛋白与mRNA表达水平均显著高于对照组（P〈0．01）;相比于顺铂组,连翘酯苷组C-jun蛋白与mRNA表达水平明显降低（P〈0．05）。结论：连翘酯苷能够通过降低c—jun的表达防护顺铂所致的耳蜗损伤。     

脑源性神经营养因子和神经生长因子对顺铂诱导的内耳毒性的保护作用

目的研究豚鼠耳蜗内脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)和神经生长因子(nerve growthfactor,NGF)在顺铂致耳中毒后的表达,并探讨其对内耳的保护作用。方法将豚鼠分成对照组、顺铂组,分别给生理盐水、顺铂腹腔注射,于注射后3、5、7天取豚鼠耳蜗行石蜡切片,进行BDNF和NGF免疫组织化学染色,观察螺旋神经节BDNF和NGF蛋白表达。结果对照组耳蜗螺旋神经节细胞中BDNF几乎不表达,NGF呈中度阳性表达。顺铂组BDNF在3天时达到高峰,以后减弱;NGF在5天时达到高峰,以后减弱。结论正常豚鼠耳蜗有中度NGF的表达,表明NGF可能对内耳的正常生理功能起重要作用。顺铂干预后螺旋神经节BDNF和NGF出现高表达,提示BDNF和NGF对顺铂诱导的螺旋神经元损伤有保护作用。     

顺铂作用下沙鼠耳蜗螺旋神经节神经元和Corti器细胞的凋亡

目的 探讨顺铂是否可引起沙鼠耳蜗螺旋神经节(spiral ganglion，SG)神经元和Corti器细胞的凋亡。方法 对沙鼠进行顺铂连续腹腔注射，每日4mg／kg体重，分别于健康对照组及给药4、5、6、7d各处死沙鼠12只，取左侧耳蜗，每组动物取10只耳蜗做平行蜗轴的石蜡切片，另2只耳蜗做底回蜗轴及基底膜超薄切片。通过末端脱氧核苷酸转移酶介导的dUTP缺口末端标记技术(terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method，TUNEL)及透射电镜检测连续用药不同时间后底回SG及Corti器的细胞凋亡情况。结果 连续应用顺铂5—7d，在透射电镜下可以观察到底回SG神经元及外毛细胞中出现凋亡特征性病理改变，TUNEL标记的石蜡切片中可见给药5d后SG和Cord器出现的阳性细胞明显高于健康对照组，给药6～7d阳性细胞进一步增加。结论 细胞凋亡是顺铂损伤沙鼠SG神经元和Cord器细胞的重要方式。     

灯盏花素对顺铂所致豚鼠耳蜗损伤的拮抗作用

目的探讨灯盏花素对顺铂致豚鼠耳毒性的拮抗作用。方法将30只豚鼠分为三组:正常对照组(A组)、实验对照组(B组)、实验组(C组),每组10只。B组和C组一次性腹腔注顺铂10 mg/kg,同时C组连续10天腹腔注射灯盏花素15 mg.kg-1.d-1,B组等时程腹腔注等量生理盐水。每组豚鼠在实验前后均行听性脑干反应(ABR)检测。在豚鼠顺铂致耳毒性模型完成并检测ABR反应阈后,用免疫组织化学方法检测4-羟基-2-壬烯醛(4-HNE)在各组动物耳蜗的表达,同时用扫描电镜观察各组豚鼠耳蜗形态。结果实验前三组豚鼠ABR反应阈差异无统计学意义(P>0.05),实验后B组和C组豚鼠ABR反应阈分别为50.12±18.45、36.32±15.63 dB SPL,均明显高于实验前,且B组显著高于C组(P<0.05),B组豚鼠听功能损伤明显重于C组。4-HNE在A组表达呈阴性,在B组和C组耳蜗表达呈阳性,且在B组的表达明显强于C组。B组耳蜗外毛细胞的损伤明显较C组重。结论 4-HNE在顺铂所致豚鼠耳蜗损伤中呈阳性表达。灯盏花素对4-HNE的形成有明显抑制作用,且能拮抗顺铂对豚鼠的耳蜗毒性,表明活性氧(ROS)在顺铂所致豚鼠耳蜗损伤中起重要作用。     

热休克蛋白70在顺铂所致豚鼠耳蜗损伤中的表达以及磷霉素钠的保护作用

目的 通过豚鼠在体实验观寨磷霉素钠对顺铂耳毒性的拮抗作用以及热休克蛋白70在耳蜗中的表达情况。方法豚鼠28只,随机分为4组:正常对照组6只;单独应用磷霉素钠组6只,磷霉素钠500mg/Kg,1日1次肌注;单独应用顺铂组8只,一次性给予顺铂15mg/Kg腹腔注射;磷霉素钠保护组8只,先肌肉注射磷霉素钠500mg/Kg,间隔30min后腹腔注射顺铂15mg/Kg。4天后处死所有动物。给药前和处死前各测听觉脑干诱发电位(ABR)1次。断头后取出听泡,固定、脱钙,常规石蜡包埋、切片。HSP70单克隆抗体免疫组化染色,光镜下观察阳性表达部位,图象处理分析系统测定灰度值。结果 单纯磷霉寨钠组ABR阈值无改变;顺铂组阈值明显升高,幅度达37.1±19.9 dBspl,P<0.001;磷霉素钠保护组阈值仅提高8.1±9.6 dBspl,同对照组相比P>0.05。HSP70表达分布在耳蜗中的Corti氏器、螺旋神经节、血管纹等处,顺铂损伤后Corti氏器和螺旋神经节细胞呈强阳性表达。从灰度值来看对照组、顺铂组与磷霉素钠保护组两两比较差异均有显著性,P<0.01或0.05。结论磷霉橐钠在一定程度上可以拮抗顺铂的耳毒性,减小ABR阈值的提高。顺铂损伤后耳蜗Corti氏器和螺旋神经节细胞HSP70呈强阳性表达,表达量与耳蜗的损伤程度一致。     

顺铂对离体培养小鼠耳蜗毛细胞钙蛋白酶表达的影响

目的：观察顺铂对离体培养小鼠耳蜗毛细胞钙蛋白酶（calpain ）表达的影响,探讨顺铂致耳蜗毛细胞凋亡的机制。方法取出生后3 d的昆明小鼠300只（600耳）,分离出耳蜗基底膜600条,体外培养24 h后,随机分为对照组和4、8、16μg／ml顺铂组,每组150条;对照组加入2ml新鲜培养基,顺铂组分别加入2 ml含不同浓度顺铂（4、8、16μg／ml）的新鲜培养基,再继续培养24 h后,应用Hoechst 33258荧光染色观察耳蜗毛细胞凋亡情况,并应用免疫荧光染色和免疫印迹（Western blot）技术检测calpain 1（μ－calpain）和calpain 2（m －calpain）在耳蜗毛细胞的表达。结果4、8、16μg／m l顺铂组耳蜗毛细胞凋亡率分别为15．63％±0．20％、38．40％±2．64％和64．24％±0．05％,均高于对照组（5．55％±0．12％）,呈现明显的量效关系;不同浓度顺铂组μ－calpain和m －cal‐pain的表达均较对照组明显增强（ P＜0．01）,且m －calpain的表达随顺铂浓度的增高而明显增强（ P＜0．01）。结论顺铂可通过calpain通路诱导小鼠耳蜗毛细胞凋亡,从而发挥毒性效应。     

Co-treatment with melanotan-II,a potent melanocortin,does not protect against cisplatin ototoxicity

Cisplatin, an important chemotherapeutic agent, has severe dose-limiting side effects including peripheral neurotoxicity and ototoxicity. Peripheral neurotoxicity can be delayed or prevented by simultaneous treatment with a class of neuropeptides known as melanocortins. Examples are ORG 2766, alpha-melanocyte stimulating hormone (alpha-MSH) and melanotan-II (MT-II). In albino guinea pigs, our group has found that ORG 2766 and alpha-MSH can also reduce cisplatin-induced ototoxicity. In this study we investigated the possibly protective effects of MT-II upon cisplatin ototoxicity. Guinea pigs, equipped with a permanent round-window electrode for electrocochleography, were treated with cisplatin (1.5 mg/kg/day intraperitoneal) and simultaneously with MT-II (30 or 3 microg/kg/day subcutaneous) or saline until a 40 dB suppression of the compound action potential (CAP) threshold (3 microV criterion) at 8 kHz occurred. This -40 dB criterion was reached after 5-18 days. Thereafter, the treatment was stopped, but electrocochleography was continued for another 4 weeks. The number of days in which the -40 dB criterion was reached in the MT-II co-treated group did not differ from the period in the saline group. Ten days after the end of the treatment a spontaneous recovery of the CAP was observed in all groups and at all frequencies, although it was more pronounced at lower frequencies. Also with respect to recovery, no differences were found between the saline and the MT-II co-treated group. Thus, in contrast with the otoprotective properties of other melanocortins, MT-II has no protective properties against cisplatin-induced ototoxicity, at least not with the doses applied here.     

Protective effect of thymoquinone against cisplatin-induced ototoxicity

The aim of this study was to investigate the potential protective effect of thymoquinone against cisplatin-induced ototoxicity. This study is a prospective, controlled experimental animal study. Experiments were performed on 30 healthy female Sprague-Dawley rats. Thirty animals were divided into three groups of 10 animals each. Group 1 received an intraperitoneal (i.p.) injection of cisplatin 15 mg/kg. Group 2 received i.p. thymoquinone 40 mg/kg/day for 2 days prior to cisplatin injection and third day i.p. cisplatin 15 mg/kg was administered concomitantly. Group 2 continued to receive i.p. thymoquinone until fifth day. Group 3 received i.p. thymoquinone 40 mg/kg/day for 5 days. Pretreatment distortion product otoacoustic emissions (DPOAE) and auditory brain stem responses (ABR) testing from both ears were obtained from the animals in all groups. After the baseline measurements, drugs were injected intraperitonally. After an observation period of 3 days, DPOAE measurements and ABR testing were obtained again and compared with the pretreatment values. There was no statistically significant difference between pre and post-treatment DPOAE responses and ABR thresholds group 2 and 3. However, group 1 demonstrated significant deterioration of the ABR thresholds and DPOAE responses. Our results suggest that DPOAE responses and ABR thresholds were preserved in the cisplatin plus TQ-treated group when compared with the group receiving cisplatin alone. According to these results, cisplatin-induced ototoxicity may be prevented by thymoquinone use in rats.     

Intracochlear administration of thiourea protects against cisplatin-induced outer hair cell loss in the guinea pig

Amelioration of cisplatin-induced side-effects is of great clinical importance. Local administration of a cytoprotective agent to the inner ear offers a possibility to prevent cisplatin-induced ototoxicity without risk of interference with the antitumour effect. The ideal substance for local administration has yet to be identified. Thiourea (TU) has unique properties that make it an interesting candidate. This study was initiated to test the hypothesis that TU given by local administration protects against cisplatin ototoxicity in the guinea pig. After baseline auditory brainstem response (ABR) assessment, the left cochlea was implanted with a microtip catheter connected to an osmotic pump filled with either 27 mg/ml TU in artificial perilymph (AP), or AP administered for the full duration of the study. Three days post-implant, animals with normal ABRs received an intravenous injection of 8 mg/kg body-weight cisplatin. Five days after the cisplatin treatment ABRs were reassessed, animals decapitated and bilateral cytocochleograms prepared. TU-treated ears demonstrated significantly lower outer hair cell (OHC) loss as compared to contralateral untreated ears, and significantly lower OHC loss compared to AP-treated ears. ABR threshold shift did not differ significantly between the two groups. It can be postulated that TU demonstrates partial protection against cisplatin-induced ototoxicity.     

硫普罗宁对顺铂所致耳毒性的保护作用

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。     

Effect of intratympanic dexamethasone administration on cisplatin-induced ototoxicity in adult guinea pigs

Objective

To evaluate the effect and safety of intratympanic dexamethasone administration on cisplatin-induced ototoxicity in adult male guinea pigs and to assess the differences between early and late protection from this ototoxicity.

Methods

Forty eight adult male guinea pigs were divided as follows: group I served as control group. Group II was subjected to intratympanic saline (subgroup IIa) or dexamethasone (subgroup IIb) injection. Group III was intraperitoneally injected with cisplatin. Groups IV and V were subjected first to intratympanic dexamethasone administration in both ears for 5 days starting 1 day and 1 h – respectively – before cisplatin intraperitoneal injection.

Results

Dexamethasone intratympanic injection revealed similar functional and structural results compared with control. Cisplatin intraperitoneal injection resulted in a profound cochlear functional and structural damage in group III. Non-significant otoprotection resulted from intratympanic dexamethasone administration one day before cisplatin. Intratympanic dexamethasone injection 1 h before cisplatin treatment resulted in a significant preservation of the functional and structural properties of the cochlea.

Conclusion

Intratympanic dexamethasone administration is a safe, easy and efficient way to protect from cisplatin ototoxicity especially when administered 1 h before cisplatin treatment.     

黄芪对顺铂耳毒性保护作用的实验研究

目的探讨黄芪是否对顺铂的耳毒性具有保护作用。方法健康SD大鼠40只随机分成4组,每组10只。对照组：生理盐水2ml／d腹腔注射6天;黄芪组：黄芪注射液5g&#183;kg^-1&#183;d。腹腔注射6天;顺铂组：顺铂4mg&#183;kg^-1&#183;d^-1腹腔注射6天;顺铂加黄芪组：腹腔注射黄芪5g&#183;kg^-1&#183;d^-1加顺铂4mg&#183;kg^-1&#183;d^-16天。用药前及用药后第7天行畸变产物耳声发射（DPOAE）检测,然后处死大鼠。每组半数动物冰冻连续切片,DNA末端转移酶介导的缺口末端标记法（TUNEL）检测毛细胞凋亡;半数动物扫描电镜观察毛细胞形态。结果顺铂组用药后DPOAE幅值下降,毛细胞受损,并可观察到凋亡细胞,与对照组及黄芪组比较差异具有显著统计学意义（P〈0．01）。顺铂加黄芪组用药后DPOAE幅值上升,毛细胞受损减轻,凋亡细胞数量减少,与顺铂组比较,差异有统计学意义（P〈0.05）.结论黄芪能有效保护耳蜗免受顺铂的耳毒性损伤。     

Systemic dexamethasone for the prevention of cisplatin-induced ototoxicity

Ototoxicity is a common side effect of cisplatin chemotherapy. This study was undertaken to determine the potential protective effects of a systemic administration of dexamethasone against cisplatin-induced ototoxicity. A prospective controlled trial conducted in an animal model. The setting was Animal care research facilities of the Montreal Children’s Hospital Research Institute. An experimental guinea pig model was used. The animals were divided as follows: group 1 (n = 10): 12 mg/kg intraperitoneal (IP) cisplatin, group 2 (n = 14): 15 mg/kg/day dexamethasone IP for 2 days followed by cisplatin 12 mg/kg IP, group 3 (n = 14): 10 mg/kg/day dexamethasone IP for 2 days, on day 3, they received cisplatin 12 mg/kg IP followed by 20 mg/kg/day dexamethasone for 2 days and group 4 (n = 5): 10 ml of saline IP twice a day for 3 days. Auditory brainstem response (ABR) threshold shifts were measured at four frequencies (8, 16, 20 and 25 kHz) for groups 1, 2 and 3. Histological changes in the organ of Corti, the stria vascularis, the spiral ligament and the spiral ganglion neurons as well as scanning electron microscopy for outer hair cells were completed. Immunohistochemistry for tumour necrosis factor-alpha (TNF-α) was performed. ABR threshold shifts were similar in all groups. Histological and scanning electron findings demonstrate that dexamethasone has greater protective effect on the stria vascularis. Systemic dexamethasone administration in a guinea pig model did not provide significant protection against cisplatin-induced ototoxicity. Dexamethasone may be useful in future applications as a complementary treatment.