药酶诱导剂对生附子急性毒性的影响

目的：考察典型肝脏细胞色素氧化酶P450酶系（肝药酶）诱导剂苯巴比妥钠干预给药对生附子毒性的影响,评价生附子毒性表现过程中的CYP450因素。方法：（1）测定小鼠单独给予生附子水煎液后的LD50;（2）测定苯巴比妥钠干预3天后,小鼠给予生附子水煎液的LD50;（3）Wistar大鼠经苯巴比妥钠（PB）干预给药3天后,十二指肠给予生附子水煎液,以出现频发室性早搏为其心脏毒性指标,观察PB干预及未干预的大鼠给予生附子后频发室性早搏发生率、出现时间及恢复率情况。结果：（1）小鼠给予生附子水煎液的LD50值为7.15g/kg,95%可信限为6.19～8.29g/（kg·d）;（2）苯巴比妥钠诱导后,小鼠给予生附子水煎液的LD50〉12.08g/（kg·d）;（3）与单用生附子水煎液相比,苯巴比妥钠诱导后可显著减少生附子水煎液致大鼠频发室性早搏的发生率（P〈0.01）,延长出现时间（P〈0.01）,缩短持续时间（P〈0.01）。结论：肝药酶诱导剂可显著降低生附子的毒性。

Effect of the Inducer of CYP450 on Acute Toxicity of Sheng-Fuzi

Objective：To observe the effect of Phenobarbital（PB）,typical inducer of CYP450,on toxicity of Sheng-Fuzi,and preliminary study of the effect of CYP450 on in-vivo metabolism of toxic components of Sheng-Fuzi.Methods：The mice were adminstrained with PB,the inducer of CYP450,for three days,caculated LD50 and observed the positive rates of frequent Ventricular Premature Beat,the appreance times and lasting times,comparing the toxic reactions of mice between the adminstrain of the water ditoction of cruid fuzi alone and the adminstrain after inducing.Results ：LD50 of the water ditoction of Sheng-Fuzi is 7.15g/kg,95% confidence interval is 6.19～8.29g/（kg·d）,LD50 of the water ditoction of Sheng-Fuzi after the inducing of PB is more than 12.08g/（kg·d）.compared with the adminstrain of the water ditoction of cruid fuzi alone,the inducing of PB can significantly decrease the rates of frequent Ventricular Premature Beat（P0.01）,prolong latent period（P0.01）,shorted the lasting times（P0.01）.Conclusion ：The inducer of cyp450 can significantly alleviate the acute toxicity of Sheng-Fuzi