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目的研究万古霉素(Vancomycin,V)大剂量一次性静脉注射对豚鼠内耳的损害。方法41只豚鼠(261～364g)随机分为4组:A组:V高剂量(16倍临床用量)266mg/kg,i.v.;B组:V中剂量(8倍临床用量)133mg/kg,i.v.;C组:生理盐水2ml,i.v.溶媒对照;D组:V高剂量500mg/kg,i.p.腹腔对照。每组动物给药前及给药后1,3,7d分别测试眼震颤时间(20圈,10秒)及听觉脑干诱发电位(ABR)的阈值,计算阈移。7d后行耳蜗基底膜铺片,观察毛细胞缺失情况。结果 (1)动物自身对照和组间对照显示,给药前后的眼震颤时间均无显著性变化;(2)A组用药后click和短纯音的平均阈移在5～13dB之间,除6kHz用药后7d外,均与溶媒对照C组差异有显著性(P<0.05);B组用药后阈移不明显,与C组差异无显著性(P>0.05);(3)D组腹腔对照组用药后只有药后3d,6kHz形成5dB暂时性阈移,其余各时间的阈移与C组的差异均无显著性;(4)组织学检查结果显示,A、B、D组动物耳蜗均未见有明显外毛细胞丢失,与C对照组的耳蜗差异均无显著性。结论一次性静脉注射8倍临床用量的万古霉素对豚鼠的前庭和耳蜗不形成损害;而16倍临床用量的静脉注射对耳蜗会形成轻度损害;近30倍临床用量的一次腹腔注射,对内耳的损害亦不明显。
Objective To study the damage to the inner ear of guinea pig induced by high dose intravenous infusion of Vancomycin (V). Methods A total of 41 guinea pigs (261 ~ 364 g) were randomly divided into 4 groups: group A: high dose of 266 mg / kg V (16 times the clinical dosage); group B: 133 mg / ; Group C: saline 2ml, iv vehicle control; D group: V high dose 500mg / kg, ip ip control. The threshold of nystagmus time (20 laps, 10 seconds) and auditory brainstem response potential (ABR) were measured before treatment and at 1, 3 and 7 days after administration respectively. 7d after cochlear basilar membrane was plated to observe the hair loss. Results (1) The self-control and inter-group control showed no significant changes of nystagmus time before and after administration. (2) The average threshold shift between clicks and short pure tones in group A was between 5 and 13 dB, except for 6 kHz (P <0.05). There was no significant difference between group C and group C (P> 0.05). (3) In group D, Group 3, 6kHz after treatment only 5dB temporary threshold shift, the rest of the time threshold shift and C group were no significant difference; (4) histological examination showed that A, B, D group were cochlear No significant loss of outer hair cells was found, and there was no significant difference between the two groups. Conclusions One-time intravenous injection of vancomycin at 8-fold clinical dose did not cause damage to the vestibule and cochlea in guinea pigs. Intravenous injection of 16-fold clinical dose resulted in mild damage to the cochlea; nearly 30-fold clinical dose of intraperitoneal injection of Damage to the inner ear is also not obvious.