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目的:预测石杉碱甲可能的药物相互作用和确保石杉碱甲 的用药安全。方法:检测石杉碱甲对肝细胞色素P450不同亚型酶活性和表达的影响。大鼠灌胃0,0.1(药理学剂量),1或2 mg/kg石杉碱甲,连续2周。苯巴比妥、3-甲基氮蒽、乙醇和地塞米松作阳性对照。制备肝细胞微粒体和总mRNA,CO差示光谱法测定总细胞色素P450含量,特异性底物代谢法测定细胞色素P450的活性,蛋白质印迹法和反转录PCR检测细胞色素450的表达。结果:0.1 mg/kg石杉碱甲对细胞色素P450的活性和表达无影响。1,2 mg/kg组大鼠肝CYP1A2活性,CYP1A2蛋白和mRNA含量增加,但与3-甲基氮蒽的诱导效应相比作用微弱。1,2 mg/kg石杉碱甲对CYP2C11,CYP2B1/2,2E1和3A活性以及表达无明显变化。结论:药理学剂量石杉碱甲对大鼠肝细胞色素P450活性和表达无影响,毒理学剂量石杉碱甲可轻微的诱导CYP1A2。石杉碱甲对CYP1A2的诱导与转录增强有关。
OBJECTIVE: To predict the possible drug interactions of Huperzine A and to ensure the safety of Huperzine A. Methods: The effect of Huperzine A on the activity and expression of different cytochrome P450 subtypes was examined. Rats were gavaged with 0,0.1 (pharmacological dose), 1 or 2 mg / kg huperzine A for 2 weeks. Phenobarbital, 3-methylanthracene, ethanol and dexamethasone as positive control. Preparation of hepatocyte microsomes and total mRNA, CO differential spectrophotometry determination of total cytochrome P450 content, specific substrate metabolite determination of cytochrome P450 activity, Western blot and reverse transcription PCR detection of cytochrome 450 expression. Results: Huperzine A at 0.1 mg / kg had no effect on the activity and expression of cytochrome P450. CYP1A2 activity and CYP1A2 protein and mRNA content in the liver of 1,2 mg / kg group increased, but the effect was weaker than the induction effect of 3-methylanthracene. Huperzine A at 1,2 mg / kg showed no significant change on the activity and expression of CYP2C11, CYP2B1 / 2, E1E and 3A. Conclusion: Pharmacological dose huperzine A has no effect on the activity and expression of hepatocyte cytochrome P450 in rats. Huperzine A can induce CYP1A2 slightly. Huperzine A is related to the induction of CYP1A2 and its transcription.