粉防己碱对豚鼠链霉素性听觉脑干反应阈值上移的干预效应

Interventional effect of tetrandrine on the shift of threshold of auditory brainstem responses induced by streptomycin in guinea pigs

目的:观察粉防己碱对豚鼠链霉素性听觉脑干反应阈值上移的干预作用。方法:实验于2003-12/2004-05在沈阳师范大学化学与生命科学学院毒理学实验室和中国医科大学听觉研究室完成。选用2月龄的健康白色红目豚鼠40只,体质量200～250g。将双耳阈值<5dB健康白色红目豚鼠采用单纯随机法分为4组:正常对照组、粉防己碱组、链霉素组、粉防己碱+链霉素组,每组10只。正常对照组:每日腹腔注射生理盐水1.5mL/kg,用pH7.4磷酸盐缓冲液1.5mL/kg灌胃。粉防己碱组:每日腹腔注射生理盐水1.5mL/kg,粉防己碱30mg/kg灌胃。链霉素组:每日腹腔注射链霉素150mL/kg,用pH7.4磷酸盐缓冲液1.5mL/kg灌胃。粉防己碱+链霉素组:每日灌注粉防己碱30mL/kg,腹腔注射链霉素150mg/kg。各组连续用药10d。在用药前1天和停药后的第1天,观察和记录4kHz和6kHz诱发的听觉脑干反应阈值。结果:40只豚鼠均进入结果分析,中途无脱落。①刺激信号为4kHz时听觉脑干反应阈值的比较:链霉素组用药后与用药前比较,差异显著(53.00±0.81,1.50±0.76,P<0.01)。粉防己碱+链霉素组停药后与用药前比较,差异亦显著(15.50±1.38,1.50±0.76,P<0.01)。两组用药后分别与正常对照组比较,差异显著(53.00±0.81,15.50±1.38,2.00±0.81,P均<0.01)。②刺激信号为6kHz时听觉脑干反应阈值的比较:链霉素组用药后与用药前比较,差异显著(35.00±1.05,0.50±0.50,P<0.01)。粉防己碱+链霉素组停药后与用药前比较,差异显著(9.00±1.00,1.50±0.76,P<0.01)。两组用药后分别与正常对照组比较,差异亦显著(35.00±1.05,9.00±1.00,1.50±0.76,P均<0.01)。结论:粉防己碱对豚鼠链霉素性听觉脑干反应阈值上移有明显的干预作用,提示粉防己碱对链霉素所致的听功能损伤有确切的拮抗作用。

AIM： To investigate the interventional effect of tetrandrine on the up shift of threshold of auditory brainstem responses induced by streptomycin in guinea pigs. METHODS： The experiment was performed at the Toxicology Laboratory, College of Chemistry and Life Science, Shenyang Normal University and Auditory Sense Laboratory of China Medical University from December 2003 to May 2004. Totally 40 healthy white red-eye guinea pigs aged 2 months, with the body mass of 200-250 g were selected. The healthy white red-eye guinea pigs with both of ears＇ threshold of auditory brainstem responses 〈 5 dB were divided into 4 groups by simple randomized blocks： normal control group, tetrandrine group, streptomycin group and tetrandrine plus streptomycin group with 10 in each group. The guinea pigs in the normal control group were treated with 1.5mL/kg saline by intraperitoneal injection every day and 1.5 mL/kg pH7.4 phosphate buffer by gastric perfusion. The guinea pigs in the tetrandrine group were given 1.5 mL/kg saline by intraperitoneal injection every day and 30 mg/kg tetrandrine by gastric perfusion. The guinea pigs in the streptomycin group received 150 mg/kg streptomycin by intraperitoneal injection every day and 15 mL/kg pH7.4 phosphate buffer by gastric perfusion. The guinea pigs in the tetrandrine plus streptomycin group were treated with 30 mg/kg tetrandrine by gastric perfusion every day and 150 mg/kg streptomycin by intraperitoneal injection. Every group received medicine for 10 days successively. The evoked threshold of auditory brainstem responses induced by 4 kHz and 6 kHz was observed and recorded before and after with the medicine. RFSULTS： Totally 40 guinea pigs were involved in the result analysis, no drop out. ①Comparison of threshold of auditory brainstem responses at 4 kHz： The difference was significant after taking medicine compared with that before taking medicine in the streptomycin group （53.00±0.81,1.50±0.76,P 〈 0.01）. The difference was significant after drug withdraw in the tetrandrine plus streptomycin group compared with that before taking medicine （15.50±1.38,1.50±0.76,P 〈 0.01）. After taking medicine the difference was significant compared with that in the normal control group （53.00±0.81,15.50±1.38,2.00±0.81 ,P 〈 0.01）. ②Comparison of threshold of auditory brainstem responses at 6 kHz： The difference was significant after taking medicine in the streptomycin group compared with that before taking medicine （35.00±1.05,0.50±0.50,P 〈 0.01）. The difference was significant after drug withdraw in the tetrandrine plus streptomycin group compared with that before taking medicine （9.00±1.00,1.50±0.76,P 〈 0.01）. The difference was significant after taking medicine compared with that in the normal control group （35.00±1.05,9.00± 1.00,1.50±0.76 ,P 〈 0.01 ）. CONCLUSION： The tetrandrine has obviously interventional effect on up shift of threshold of auditory brainstem responses induced by streptomycin in guinea pigs, which indicates that the tetrandrine has definite antagonistic effect on injury of auditory function induced by streptomycin.