Backous D D, Henley C M, Dunn J K, Jenkins H A
Clayton Neurotology Laboratory, Department of Otorhinolaryngology and Communicative Sciences, Baylor College of Medicine, Houston, TX 77030.
Otolaryngol Head Neck Surg. 1994 Oct;111(4):377-84. doi: 10.1177/019459989411100401.
Biochemical and pharmacologic studies suggest a role for the ornithine decarboxylase-polyamine system as a modulator of behavioral changes during vestibular compensation. alpha-Difluoromethylornithine specifically blocks the rate-limiting step of polyamine biosynthesis. To assess the effects of alpha-difluoromethylornithine on the acute phase of postural compensation, guinea pigs were divided into groups subjected to either unilateral labyrinthectomy only (n = 7), alpha-difluoromethylornithine (500 mg/kg/day) for 4 days before labyrinthectomy (n = 10), equivalent volumes of saline for 4 days before labyrinthectomy (n = 8), and sham operations (n = 5). Yaw head tilt and roll head tilt, trunk curvature, and air-righting reflex were measured at baseline and at regular intervals up to 4 weeks. alpha-Difluoromethylornithine significantly delayed recovery of normal air-righting but had no effect on yaw head tilt, roll head tilt, and trunk curvature. We also evaluated effects of alpha-difluoromethylornithine in compensated guinea pigs. Fully compensated animals from phase 1 were randomly assigned to receive alpha-difluoromethylornithine (500 mg/kg/day) or saline once daily for 4 days. Only 33% of alpha-difluoromethylornithine animals maintained air-righting, compared with 100% of saline-treated animals (p = 0.003). Maximum trunk curvature was greater in the alpha-difluoromethylornithine group (p = 0.02). Thus alpha-difluoromethylornithine not only delayed the time course for postural recovery after unilateral labyrinthectomy, it also transiently disrupted the maintenance of the compensated state.
生化和药理学研究表明，鸟氨酸脱羧酶-多胺系统在前庭代偿过程中作为行为变化的调节因子发挥作用。α-二氟甲基鸟氨酸特异性阻断多胺生物合成的限速步骤。为了评估α-二氟甲基鸟氨酸对姿势代偿急性期的影响，将豚鼠分为仅接受单侧迷路切除术的组（n = 7）、在迷路切除术前行4天α-二氟甲基鸟氨酸（500 mg/kg/天）处理的组（n = 10）、在迷路切除术前行4天等量生理盐水处理的组（n = 8）以及假手术组（n = 5）。在基线时以及直至4周的定期时间点测量偏航头倾斜、侧滚头倾斜、躯干弯曲和空中翻正反射。α-二氟甲基鸟氨酸显著延迟了正常空中翻正的恢复，但对偏航头倾斜、侧滚头倾斜和躯干弯曲没有影响。我们还评估了α-二氟甲基鸟氨酸对已代偿豚鼠的影响。将来自第1阶段的完全代偿动物随机分配，每天接受一次α-二氟甲基鸟氨酸（500 mg/kg/天）或生理盐水，持续4天。与100%接受生理盐水处理的动物相比，仅33%接受α-二氟甲基鸟氨酸处理的动物维持了空中翻正能力（p = 0.003）。α-二氟甲基鸟氨酸组的最大躯干弯曲更大（p = 0.02）。因此，α-二氟甲基鸟氨酸不仅延迟了单侧迷路切除术后姿势恢复的时间进程，还短暂破坏了代偿状态的维持。
