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目的研究甘草提取物对中毒剂量马钱子碱的药代动力学影响。方法大鼠随机分为模型组、对照组和低、中、高3个剂量实验组,每组8只。模型组腹腔注射马钱子碱40 mg·kg~(-1);高、中、低3个剂量实验组于马钱子碱腹腔注射后分别给予甘草提取物18,0.45,0.18 g·kg~(-1);对照组于腹腔注射马钱子碱后立刻给予葡醛内酯60 mg·kg~(-1)。第一次给药后0,8.33×10~(-2),0.25,0.5,0.75,1,2,3,5,7,9,11,24 h眼眶采血获得大鼠血浆,以HPLC-MS/MS法测定马钱子碱血浆浓度。用DAS软件处理数据,计算各组药代动力学参数。结果模型组马钱子碱的Cmax为(4818.37±665.90)ng·mL~(-1),AUC_(0-∞)为(6296.73±875.14)ng·h·m L~(-1),t_(1/2)为(3.25±1.28)h。低剂量实验组马钱子碱的药代动力学未发生明显改变;高、中剂量实验组较模型组C_(max)分别降低了19.1%和23.5%;t_(1/2)分别缩短了45.5%和48.5%;平均驻留时间(MRT)分别缩短了44.7%和46.8%(P<0.05)。葡醛内酯处理对马钱子碱药代动力学无明显影响。结论一定浓度范围内,甘草提取物能明显降低马钱子碱的峰浓度和半衰期,这可能是甘草缓解马钱子碱毒性的重要机制。
Objective To study the effect of licorice extract on the pharmacokinetics of brucine in poisoning dose. Methods The rats were randomly divided into model group, control group and low, medium and high doses of three experimental groups, each group of eight. The model group was given intraperitoneal injection of brucine 40 mg · kg -1. The high, middle and low doses of the experimental group were injected with brucine after intraperitoneal injection of licorice extract 18,0.45,0.18 g · kg ~ (-1). The control group received glucurolactone 60 mg · kg -1 immediately after intraperitoneal injection of brucine. After the first administration, blood was collected from orbital blood of 0,8.33 × 10 ~ (-2), 0.25,0.5,0.75,1,2,3,5,7,9,11,24 h, / MS determination of brucine plasma concentration. Data were processed using DAS software and pharmacokinetic parameters were calculated for each group. Results The Cmax of strychnine in the model group was (4818.37 ± 665.90) ng · mL -1, the AUC_ (0-∞) was 6296.73 ± 875.14 ng · h · m L -1, t_ 1/2) was (3.25 ± 1.28) h. The pharmacokinetics of brucine in the low-dose experimental group did not change significantly; the C max of experimental group were reduced by 19.1% and 23.5% respectively compared with the model group; the t 1/2 was shortened by 45.5 % And 48.5%, respectively. Mean duration of stay (MRT) decreased by 44.7% and 46.8%, respectively (P <0.05). Glucurolactone treatment had no significant effect on strychnine pharmacokinetics. Conclusion Licorice extract can significantly reduce the peak concentration and half-life of brucine within a certain concentration range, which may be an important mechanism of glycyrrhizin to ease the toxicity of strychnine.