头孢哌酮钠和卡那霉素在豚鼠化脓性中耳炎中的作用及耳毒性机制研究

Pharmacological effects and Ototoxicity Mechanism of cefoperazone sodium and Kanamycin on Suppurative otitis media in the guinea pigs

目的探讨头孢哌酮钠和卡那霉素在豚鼠化脓性中耳炎中的作用、耳毒性。方法 A、B、C组均应用金黄色葡萄球菌菌苗中耳腔注射法制备化脓性中耳炎模型。然后分别应用生理盐水、头孢哌酮钠滴耳液和卡那霉素滴耳液中耳腔给药治疗,各0.2 ml/次,2次/天,连续给药7天。听性脑干反应(ABR)检测豚鼠鼓室内注射金黄色葡萄球菌前后以及抗生素滴耳后ABR阈值。脓性分泌物评分和菌落计数。耳蜗基底膜铺片:毛细胞计数和形态学观察。结果 A组(生理盐水组)、B组(头孢哌酮钠组)、C组(卡那霉素组)实验后ABR听阈分别为(46.00±5.1)dB peSPL(peSPL:等效峰值声压级),(35.25±4.9)dB peSPL,(42.25±5.2)dB peSPL(差别主要是给药后,造模前后无差别)。脓性分泌物评分分别为A组(2.33±0.4)、B组(1.65±0.4)、C组(1.53±0.3)。细菌培养计数分别为A组(117±10.5)、B组(63±6.9)、C组(49±6.1)。A组和B组毛细胞未见缺失,纤毛和表皮板完好,结构正常,C组毛细胞大片缺失,相应部位的纤毛和表皮板也见缺失。结论头孢哌酮钠滴耳液的抗菌效应可以应用于化脓性中耳炎的治疗,且无耳毒性。卡那霉素滴耳液虽然抗菌效应强,但耳毒性较强,所以不推荐作为治疗化脓性中耳炎的一线用药。

Objective To explore the pharmacodynamic effects of cefoperazone sodium and kanamycin on suppurative otitis media in guinea pigs,and their ototoxicity.Methods Auditory brainstem response（ABR） was used to detect the hearing threshold before and after the modeling as well as during the whole period of experiment.The infiltrating status of inflammatory cells in middle ear mucosa was evaluated by optical microscopy.Meanwhile,bacterial flora were counted at the end of the culturing period.The changes and number of hair cells were observed by surface preparation technique of the basilar membrane.Results The ABR threshold in group A（saline group） was（46.00±5.1） dB peSPL,group B（cefoperazone sodium group）（35.25±4.9） dB peSPL,and group C（kanamycin group）（42.25±5.2） dB peSPL,respectively.The infiltrating status of inflammatory cells in middle ear mucosa was（2.33±0.4） in group A,（1.65±0.4） in group B and（1.53±0.3） in group C.Bacterial flora were（117±10.5） in group A,（63±6.9） in group B and（49±6.1） in group C.The hair cells were intact in group A and group B,but sevevely damated in group C.Conclusion Cefoperazone sodium ear drops can be used to effectively treat suppurative otitis media with its anti-bacterial effects but without ototoxicity.Although kanamycin ear drops have strong anti-bacteria effects,it has severe ototoxicity.Therefore,we consider that kanamycin ear drops can not be used as an antibiotic of choice.