探针药物评价大黄苷元对P450酶CYP1A2活性的影响

Aglycone from Rhei Radix et Rhizoma of Probe Drugs for Detecting Influences on CYP1A2 Activity by Rhubarb Aglycone

摘要:

目的: 研究大黄苷元对大鼠细胞色素P450酶(cytochrome P450,CYP450)中CYP1A2活性的影响。方法: 将SD大鼠60只随机分为12组,即空白组,苯巴比妥钠组(PB),地塞米松组(DEX),β-奈黄酮组(β-NF),酮康唑组(KET),大黄苷元不同剂量组;空白组ig给予0.5%羧甲基纤维素钠(CMC-Na),PB,DEX,β-NF三诱导剂组分别给予苯巴比妥钠注射液75 mg·kg^-1,地塞米松80 mg·kg^-1,β-奈黄酮75 mg·kg^-1,KET抑制剂组给予酮康唑82.5 mg·kg^-1,大黄苷元不同剂量组分别给予不同剂量大黄苷元(7.08,14.40,30.82,46.55,51.63,61.63,100.07 mg·kg^-1)。以非那西丁为探针药物,制得肝微粒体进行孵化实验,样品经处理后,进行高效液相测定其代谢产物对乙酰氨基酚的生成量,研究大黄苷元对CYP1A2活性的影响及给药剂量与其活性的关系。结果: 与空白组、KET给药组对比,大黄苷元61.63,30.82,14.40 mg·kg^-1组与对乙酰氨基酚的生成量有显著差异(P<0.05),其诱导效应明显弱于PB组,DEX给药组,β-NF给药组,且随着大黄苷元给药剂量(7.08,14.40,30.82,46.55,51.63,61.63,100.07 mg·kg^-1)的增加,对乙酰氨基酚的生成量有增多的趋势。结论: 大黄苷元对CYP1A2有诱导作用,且随其剂量的增加,作用呈增强趋势。

Abstract:

Objective: To study the aglycone from Rhei Radix et Rhizoma(AR) on liver microsomal P450 isozymes/cytochrome P450 (CYP450) CYP1A2 activity in rats by enzyme assays. Method: Sixty SD rats were randomly divided into the control group, the phenobarbital sodium (PB) group (75 mg·kg^-1 0.5% sodium carboxyl methyl cellulose, CMC-Na), the dexamethasone (DEX) group (80 mg·kg^-1), the beta-naphthoflavone(β-NF) group (75 mg·kg^-1), the ketoconazole(KET) group (82.5 mg·kg^-1) and the different doses of AR groups (7.08, 14.40, 30.82, 46.55, 51.63, 61.63, 100.07 mg·kg^-1). The experiment was performed in the liver microsome and the phenacetin was taken as the probe drug. The acetaminophen concentrations were determined by HPLC and the relationship between CYP1A2 activity and the dosage was conducted. Result: Compared with CMC-Na group and the KET group, the production of acetaminophen was very different in the AR groups at 61.63, 30.82, 14.40 mg·kg^-1 (P<0.05). The induce effect was much weaker than three kinds of induction agents, and it was enhanced with the increasing of the dosage. Conclusion: The AR could induce the activity of CYP1A2 in a dose-dependent manner.