用抗癫痫药物建立大鼠肝损伤的动物模型

目的 探讨抗癫痫药苯巴比妥、卡马西平对大鼠肝脏组织学及牛化指标的影响,建市抗癫痫药引起肝损伤的动物模型.方法 将7～8周龄Wistar大鼠随机分为4组,阳性对照组经腹腔注射四氯化碳（CCl4）原液1mL·kg-1.给药组,分别每日1次经口灌胃给予苯巴比妥（52.08mg·kg-1）,卡马西平（125.00mg·kg-1）,阴性对照组给予等体积的蒸馏水.每周采血检测血清生化指标,连续用药5周后,采血检测血清生化指标,应用光镜进行肝脏病理学研究.结果 （1）病理组织学检查,光镜下阳性对照组大鼠可见广泛的水性样变、空泡样变;苯巴比妥组大鼠可见部分水性样变,肝窦轻度水肿;卡马西平组大鼠可见水性样变.（2）与阴性对照组比较,苯巴比妥组、卡马西平组的肝脏指数有非常显著性差异（P〈0.01）.（3）与阴性对照组比较,苯巴比妥组、卡马西平组的血清丙氨酸氨基转移酶有显著性变化.结论 在治疗剂量范围内,连续服用抗癫痫药苯巴比妥、卡马西平5周可引起机体抗氧化能力降低,肝组织病理学检查可见轻微病理改变,引起大鼠肝损伤.

Rat Model of Liver Iniury Induced by AEDs

Objective To investigate the effects of Phenobarbital and Carbamazepine on hepatic injury via the observations of pathohistology and biochemical indicators in Wistar rats.Methods Wistar rats were randomly divided into four groups： Phenobarbital group,Carbamazepine group,the negative control group and the positive control group （8 for each group）.The rats in four experimental groups were administered intragastrically with 52.08mg·kg^-1 of Phenobarbital,125.00mg·kg^-1 of Carbamazepine once a day respectively.The negative control group were administered intragastrically with the same volume distilled water respectively.The rats in the positve control group were treated by peritoneal injection of lmL·kg^-1 carbon tetrachloride（CC14）.Every week biochemical indicators in serum was examined.After 5 weeks,liver pathohistology was observed under the light microscope and liver homogenate was examined. Results （1） Extensive steatosis and diffuse punctated necrosis of hepatocytes distributed in the portal area could be found under the light microscope in the positive control group.There were steatosis of partial hepatocytes in the Phenobarbital group and Carbamazepine group.（2） There was significantly difference of the hepatic index in Phenobarbital group and Carbamazepine group which compared with the negative control group.（3） Compared with the negative control group,the levels of serum alanine aminotransferase（ALT） in Phenobarbital group and Carbamazepine group were significantly increased. Conclusions In therapeutic doses,long-term use of Phenobarbital and Carbamazepine can be associated with decreased antioxidant capacity of organism and slight pathological changes in liver.