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马钱子碱每日低、中、高(3,15和60 mg·kg-1)剂量以及高剂量马钱子碱和甘草次酸(每日25 mg·kg-1)、甘草苷(每日20 mg·kg-1)配伍,分别对Wistar大鼠连续灌胃给药7天后,检测不同给药组对CYP3A、CYP1A2、CYP2E1和CYP2C的酶活性和mRNA表达的影响。与对照组相比,高剂量马钱子碱使CYP3A活性下降24.5%,CYP2C的活性下降34.6%,而使CYP2E1的活性提高了146.1%。另一方面,与高剂量组相比,甘草次酸配伍组使CYP2E1的活性降低了51.4%,CYP1A2的活性降低了33.5%;甘草苷配伍组使CYP2E1的活性降低了41.1%,CYP2C的活性降低了37.7%。实验结果表明,马钱子碱和甘草次酸、甘草苷配伍后,可以在一定程度上影响上述CYP450酶的mRNA表达和酶活性。因此推测配伍后甘草苷对马钱子碱所致CYP450酶异常变化的拮抗作用,以及甘草次酸对CYP2E1和CYP1A2活性的抑制作用,可能是甘草降低马钱子毒性的重要机制之一。
Strychnine daily low, medium and high (3,15 and 60 mg · kg-1) doses and high-dose strychnine and glycyrrhetinic acid (25 mg · kg-1 daily), glycyrrhizin Day 20 mg · kg-1). After 7 days of continuous intragastric administration to Wistar rats, the effects of different administration groups on the enzyme activity and mRNA expression of CYP3A, CYP1A2, CYP2E1 and CYP2C were detected. Compared with the control group, high-dose brucine reduced CYP3A activity by 24.5%, CYP2C activity by 34.6%, and CYP2E1 activity by 146.1%. On the other hand, compared with the high-dose group, glycyrrhetinic acid combined group decreased the activity of CYP2E1 by 51.4% and the activity of CYP1A2 by 33.5%, while the combination of liquiritin and glycyrrhizin reduced the activity of CYP2E1 by 41.1% and the activity of CYP2C 37.7%. The experimental results show that the strychnine and glycyrrhetinic acid, glycyrrhizin compatibility, to a certain extent, affect the CYP450 enzyme mRNA expression and enzyme activity. Therefore, it is speculated that the antagonistic effect of glycyrrhizin on the abnormal changes of CYP450 enzyme induced by brucine and the inhibitory effect of glycyrrhetinic acid on the activity of CYP2E1 and CYP1A2 may be one of the important mechanisms by which licorice can reduce the toxicity of brucine.