吴茱萸有效部位对大鼠肝脏5种CYP450亚酶mRNA的影响

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目的:制备吴茱萸挥发油、总黄酮及总生物碱等有效部位,对大鼠诱导后取肝脏,采用实时荧光定量PCR法考察大鼠肝脏5种CYP450亚酶mRNA的影响。方法:吴茱萸药材以水-乙醇提取,经挥发油提取器制备吴茱萸挥发油,药液浓缩、干燥后制备吴茱萸提取物,提取物经聚酰胺色谱柱分离得总黄酮,经酸提碱沉法制备总生物碱。将雄性SD大鼠分为5组,以生理盐水组为空白对照,连续灌胃诱导7 d后解剖取肝脏,采用实时荧光定量PCR法评价空白组、挥发油组、黄酮组、生物碱组以及提取物组肝脏CYP450亚酶的mRNA表达。结果:吴茱萸挥发油类成分对大鼠肝脏的CYP3A1、CYP2B1的mRNA表达均具有抑制作用,黄酮类成分对CYP2B1具有非常显著抑制作用,生物碱类成分对CYP2E1、CYP3A1具有抑制作用,吴茱萸总提取物对CYP2B1具有抑制作用。结论:从基因水平考查了吴茱萸对大鼠肝脏5种CYP450亚酶的影响,提示在吴茱萸的临床使用中应注意代谢性相互作用和药物不良反应。 OBJECTIVE: To prepare effective fractions of volatile oil, total flavonoids and total alkaloids from Evodia rutaecarpa, to induce the livers in rats, and to examine the effects of 5 CYP450 mRNAs in the liver by real-time fluorescence quantitative PCR. Methods: Evodia rutaecarpa medicinal materials were extracted with water and ethanol, and the essential oil of Evodia rutaecarpa was prepared by volatile oil extractor. The liquid was concentrated and dried to prepare Evodia rutaecarpa extract. The total flavonoids were extracted from the extract by polyamide column and the total organism Alkali. The male SD rats were divided into 5 groups. The rats in the normal saline group were used as blank control. After 7 days of continuous gavage, the liver was dissected and the blank group, volatile oil group, flavonoid group and alkaloid group were extracted by real-time fluorescence quantitative PCR The mRNA expression of CYP450 subunit in the liver of rats. Results: The constituents of volatile oil of Evodia rutaecarpa inhibited the mRNA expression of CYP3A1 and CYP2B1 in liver of rats, the flavonoids had a significant inhibitory effect on CYP2B1, the alkaloids inhibited the activities of CYP2E1 and CYP3A1, the total extract of Evodia CYP2B1 has an inhibitory effect. Conclusion: The effects of Evodia rutaecarpa on five kinds of CYP450 subunits in rat liver were investigated at the gene level, which indicated that metabolic reactions and adverse drug reactions should be noticed in the clinical use of Evodia rutaecarpa.
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