沙棘黄酮对大鼠肝脏CYP450酶mRNA表达的影响

Effect of Hippophae Rhamnoides Flavonoids on mRNA Expression of CYP450 Enzyme in Rat Liver

目的:研究沙棘黄酮对CYP2d2、CYP2b1、CYP2c11和CYP2e1 mRNA表达的影响。方法:根据随机原则,将40只雄性大鼠分为空白对照组、阳性对照组、沙棘黄酮高剂量组、中剂量组和低剂量组。给药组分别灌胃400、200和100 mg/kg的沙棘黄酮提取物,空白对照组灌胃等容量蒸馏水,连续14d;阳性对照组从第8天开始腹腔注射苯巴比妥钠50 mg/kg,连续7d。给药结束后,检测大鼠血清生化指标,并采用实时荧光定量PCR方法测定各实验组大鼠肝脏CYP2c11、CYP2e1、CYP2d2和CYP2b1 mRNA的表达。结果:与空白对照组相比,各给药组谷丙转氨酶(ALT)、谷草转氨酶(AST)、总蛋白(TP)、球蛋白(GLB)、白蛋白(ALB)和肝重/体重比(L/W)未发生显著性改变,中剂量和低剂量组直接胆红素(DBIL)显著降低;高剂量组CYP2d2的mRNA表达显著上调,各给药组对CYP2b1,CYP2c11和CYP2e1的mRNA表达没有影响。结论:沙棘黄酮可以上调CYP2d2 mRNA的表达,提示沙棘黄酮可以调节大鼠CYP2d2酶的活性,即沙棘黄酮可能会诱导人CYP2D6酶的活性。当沙棘或沙棘黄酮与经CYP2D6代谢的药物合用时,可能发生草药-药物相互作用。因此,在临床实践中应给予足够的重视。

Objective:To study the effect of seabuckthorn flavonoids on the expression of CYP2d2,CYP2b1,CYP2c11 and CYP2e1 mRNA.Methods:According to the principle of random allocation,40 male rats were divided into blank control group,positive control group,high-dose seabuckthorn flavone group,medium-dose group and low-dose group.The treatment group was given 400,200 and 100 mg.kg-1 of sea buckthorn flavone extract,the blank control group was given the same amount of distilled water,and each group was given continuous administration for 14 days;the positive control group was intraperitoneally injected with phenobarbital Sodium 50 mg.kg-1 from the 8th day.After administration,serum biochemical indexes were detected,and the mRNA expressions of CYP2c11,CYP2e1,CYP2d2 and CYP2b1 in the liver of rats in each group were determined by real-time quantitative PCR method.Results:Compared with blank control group,ALT,AST,TP,GLB,ALB and L/W values in administration groups did not change significantly,while DBIL in medium and low dose groups was significantly decreased;the mRNA expression of CYP2d2 was significantly up-regulated in the high-dose group,while the mRNA expression of CYP2b1,CYP2c11 and CYP2e1 were not affected by each administration group.Conclusion:Hippophae rhamnoides flavonoids can up-regulate the expression of CYP2d2 mRNA,suggesting that seabuckthorn flavonoids can induce the activity of CYP2d2 in rats,that is,seabuckthorn flavonoids may induce the activity of CYP2D6 in humans.Herb-drug interactions may occur when seabuckthorn or seabuckthorn flavonoids are used in combination with drugs metabolized by CYP2D6.Therefore,sufficient attention should be paid in clinical practice.