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目的:考察长期口服苯妥英锌(phenytoinzinc,PZ)对幼年家兔小脑生长发育的影响。方法:1月龄新西兰家兔分别给予PZ或苯妥英钠(phenytoinsodium,PS)7个月(剂量分别为:30、10mg·kg-1·d-1),药前、药中(4个月)和药后进行三次CT扫描,测量小脑最大横径和蚓部最大横径。服药结束后处死动物,Bouin氏液灌注固定脑组织,测定全脑的长、宽和高以及重量。结果:CT扫描显示PS组服药4个月和7个月后,小脑最大横径分别缩短14.0%(P<0.05)和32.2%(P<0.01);蚓部最大横径分别缩短16.4%(P<0.05)和30.8%(P<0.01)。PZ组仅在服药7个月后,小脑和蚓部的最大横径比对照组分别缩短16.1%(P<0.05)和19.7%(P<0.05)。固定后的小脑和蚓部的长度和宽度,PS组均比对照组明显缩短;全脑湿重和乙醇脱水后重量以及小脑重量与对照组比较均显著减轻,其中全脑脱水后重量减轻15.4%(P<0.05),小脑重量减轻18.4%(P<0.05)。而PZ组的上述测定值与对照组均无显著性差异。结论:幼兔长期口服高剂量PS后导致小脑萎缩,而口服PZ后对小脑的形态影响比PS轻,有可能降低本类抗癫痫药物长期服用后引起的小脑萎缩。
Objective: To investigate the effects of chronic oral administration of phenytoinzinc (PZ) on cerebellum growth in young rabbits. Methods: New Zealand rabbits (1 month old) were given PZ or phenytoinsodium (PS) for 7 months (dose: 30 and 10 mg · kg-1 · d-1, respectively) Three times after drug and CT scan to measure the maximum transverse diameter of cerebellum and vermis Department of the largest diameter. The animals were sacrificed at the end of the treatment, and brain tissue was perfused with Bouin’s solution to measure the length, width, height, and weight of the whole brain. Results: CT scan showed that the maximum transverse diameter of cerebellum was shortened by 14.0% (P <0.05) and 32.2% (P <0.01), and the maximum diameter of vermis was reduced by 16.4% (P <0.05) and 30.8% (P <0.01). After 7 months of treatment, the maximum diameter of cerebellum and vermis in the PZ group decreased by 16.1% (P <0.05) and 19.7% (P <0.05), respectively, compared with the control group. After fixation, the length and width of cerebellum and vermis were significantly shorter in PS group than those in control group. The weight of whole brain and ethanol dehydration and cerebellar weight were significantly reduced compared with control group, and the weight loss of whole brain after dehydration was 15.4% (P <0.05), and cerebellar weight decreased by 18.4% (P <0.05). The PZ group of the above measured values and the control group no significant difference. CONCLUSION: Long-term oral administration of high-dose PS in rabbits leads to cerebellar atrophy. However, morphological changes of cerebellum after oral administration of PZ are less severe than those of PS, which may reduce cerebellar atrophy caused by long-term use of antiepileptic drugs.