中文摘要：

目的：研究甘草酸对中毒剂量下马钱子碱血浆、脑组织药动学的影响,探讨甘草酸解毒机制。方法：3组小鼠分别连续7 d腹腔注射生理盐水、甘草酸溶液和维拉帕米溶液,第8天均腹腔注射马钱子碱溶液。UPLC-MS/MS法测定血浆和脑组织匀浆液中马钱子碱浓度。实时荧光定量PCR技术分析脑组织中P-gp编码基因mdr1a表达水平。结果：持续给予甘草酸使脑/血浓度比值曲线下面积较对照组减少37.6%（P〈0.05）,并可诱导小鼠脑组织mdr1a mRNA的表达。P-gp抑制剂维拉帕米使脑内AUC0→10 h、脑/血浓度比值曲线下面积分别增加了30.7%,32.5%（P〈0.05）。结论：甘草酸可能通过诱导血脑屏障上P-糖蛋白加速马钱子碱的脑部转运,维拉帕米阻止了马钱子碱从脑部的排出,马钱子碱可能是小鼠血脑屏障上P-gp底物。

英文摘要：

OBJECTIVE To investigate the effects of glycyrrhizic acid on the kinetics of metabolism for toxic dosage of brucine in plasma and brain,and explore a new antidotal pathway for brucine-induced toxicity.METHODS Male KM mice were injected intraperitoneally with normal saline,glycyrrhizic acid and verapamil for 7 days,respectively.In the 8th day,each animal was injected intraperitoneally with brucine.UPLC-MS/MS method and real-time fluorescence quantitative RT-PCR methods were used to determinate the brucine＇s concentration and the expression of mdr1a,respectively.RESULTS After treatment with glycyrrhizic acid,the AUC0→10h of brain/plasma concentration ratio decreased 37.6% compaered to control group（P0.05）.The RT-PCR results revealed that continuesly treated with glycyrrhizic acid could induce the expression of mdr1a mRNA in the brain of mice.The AUC0→10h and the AUC0→10h of brain/plasma concentration ratio increased 30.7%,32.5% respectively by verapamil（P0.05）.CONCLUSION The experiment proved that glycyrrhizic acid may accelerate the elimination of brucine through up-regulate the P-gp＇s function in the brain of mice.Verapamil could reverse the decreased trend of drug disposition in brain,so brucine may be the substrate of P-gp in blood-brain barrier.