【摘要】 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。更多还原

【Abstract】 AIM: To predict possible drug interaction and assure safety medication of huperzine A (HupA). METHODS: The effects of HupA on activities and expressions of cytochrome P-450 (CYP) were examined. Liver microsomes and total mRNA were prepared from rats treated orally with 0, 0.1 (pharmacological dose), 1, or 2 mg/kg huperzine A for 2 weeks. Phenobarbital, 3-methylcholanthrene (3-MC), ethanol, and dexamethasone were used as positive controls. Total CYP protein was assayed by carbon monoxide difference spectrum. Activity of isoenzyme was detected with specific probe. Expression of CYP protein and mRNA was analyzed with Western blot and RT-PCR. RESULTS: No changes of isoenzyme expression and catalytic activities were found in rats treated with 0.1 mg/kg huperzine A. Huperzine A 1, 2 mg/kg parallelly increased CYP1A2 activity, protein and mRNA, although they were minor when contrasted with 3-MC. Huperzine A 1, 2 mg/kg got no effects on CYP2C11, CYP2B1/2, 2E1 and 3A. CONCLUSION: Activity and expression of liver CYP isoenzymes were not affected in rats treated with pharmacological dose of HupA, but HupA at toxicological dose may elicit a slight inductive response of CYP1A2. The CYP1A2 induction produced by HupA is related to transcription enhancement.更多还原