鼓室注射地塞米松拮抗顺铂耳毒性的研究

The Protective Effects of Intratympanic Dexamethasone to Prevent Cisplatin Ototoxicity

目的探讨鼓室注射地塞米松对顺铂致听觉损伤的保护作用。方法将55只豚鼠分为4组:正常对照组(I组)10只,腹腔注射生理盐水16ml/kg;地塞米松组(II组)15只,经鼓室注射地塞米松10mg/ml;顺铂组(III组)15只,单次腹腔注射顺铂16mg/kg;顺铂+地塞米松组(IV组)15只,经鼓室注射地塞米松10mg/ml,1小时后腹腔注射顺铂16mg/kg。给药前及给药后第7天测试各组豚鼠听性脑干反应(auditory brainstem response,ABR),并检测耳蜗组织丙二醛(malondiadehyde,MDA)含量和超氧化物歧化酶(superoxide dismutase,SOD)活性。结果 I^IV组给药前ABR反应阈分别为28.50±4.74、28.67±5.82、26.67±4.88和27.33±5.30dB nHL,差异无统计学意义(P>0.05);给药后I组和II组ABR反应阈分别为29.00±3.94和31.33±5.81dB nHL,给药前后差异无统计学意义(P>0.05);给药后III组和IV组ABR反应阈为55.33±4.81、40.67±3.72dB nHL,均显著高于给药前(P<0.05),但IV组ABR反应阈低于III组(P<0.05)。给药后I组MDA含量和SOD活性分别为2.01±0.07mmol/L和234.10±13.09U/ml,II组分别为2.06±0.09mmol/L和233.20±13.24U/ml,两组比较差异无统计学意义(P>0.05),III、IV组MDA含量分别为5.74±0.17、3.51±0.18mmol/L,显著高于I、II组(均为P<0.05),但IV组MDA含量显著低于III组(P<0.001);III、IV组SOD活性分别为107.90±14.21、162.70±11.25U/ml,明显低于I、II组(均为P<0.05),但IV组的SOD活性显著高于III组(P<0.001)。结论鼓室注射地塞米松对顺铂耳毒性具有一定的拮抗作用。

Objective To investigate the effectiveness of intratympanic dexamethasone injection as a protection agent against cisplatin ototoxicity.Methods Fifty five healthy guinea pigs were randomly divided into four groups.The guinea pigs groups received（group I）0.9% NaCl solution（16ml/kg）intraperitoneally（IP）,（group II）dexamethasone（10mg/ml）intratympanically（IT）,（group III）cisplatin（16mg/kg）only intraperitoneally（IP）and（group IV）dexamethasone（10mg/ml）IT followed after 1hby 16mg/kg cisplatin.Before and 7days following injections,the ototoxic effect was measured with auditory brainstem response（ABR）.The contents of malondiadehyde（MDA）and activities of superoxide dismutase（SOD）were also measured.Results ABR thresholds before and after dosing were 28.50±4.74,29.00±3.94 dB nHL and 28.67±5.82,31.33±5.81 dB nHL in group I and group II,respectively,with no significant differences（P〉0.05）.The contents of MDA and activities of SOD were 2.01±0.07mmol/L,234.10±13.09U/ml and 2.06±0.09mmol/L,233.20±13.24U/ml in the group I and group II,respectively,with no significant differences（P〉0.05）.ABR thresholds after dosing were 55.33±4.81,and 40.67±3.72 dB nHL in the group III and group IV,which were significantly increased,but ABR thresholds in the group IV were significantly lower than that in the group III（P〈0.05）.The contents of MDA were 5.74±0.17,3.51±0.18mmol/L in the group III and group IV,which were significantly increased.SOD activities were 107.90±14.21,and 162.70±11.25U/ml,which significantly decreased.Nevertheless,in the group IV dexamethasone relatively reduced the contents of MDA（P〈0.001）while increased the activities of SOD（P〈0.001）compared with group III.Conclusion Intratympanic dexamethasone injection presents as an effective treatment modality to prevent cisplatin ototoxicity without any ototoxic effect.