微透析技术结合液质联用的不同黄芪剂量的补阳还五汤在脑缺血损伤大鼠血药动学研究

目的：探讨不同黄芪剂量的补阳还五汤益气组与活血组有效成分在MCAO大鼠体内的药动学特征。方法：复制大鼠脑缺血再灌注动物模型,建立补阳还五汤微透析样品的液质联用检测方法,研究补阳还五汤益气组低、中、高剂量（3.09,6.17,12.34 g·kg^-1）,活血组注射液给药剂量为2.32 g·kg^-1,股静脉给药后脑缺血再灌注损失大鼠中有效成分的药动学特征。结果：补阳还五汤不同给药组中芒柄花素和芍药苷血液药动学过程符合一房室模型,低剂量益气组和活血组中芒柄花素和芍药苷的半衰期（t_1/2）分别为（46.89±1.77）,（25.47±1.43）min,平均滞留时间（MRT）分别为（67.66±2.55）,（36.74±2.07）min,药-时曲线下面积（AUC_0-t）分别为（39 325.21±7 411.43）,（225 496.40±24 990.38）ng·mL^-1·min;中剂量益气组和活血组中芒柄花素和芍药苷的t_1/2分别为（43.73±0.47）,（26.24±1.10）min,MRT分别为（63.09±0.68,37.85±1.59）min,AUC_0-t（67 556.41±7 043.40）,（242 206.10±19 296.12）ng·mL^-1·min;高剂量益气组和活血组中芒柄花素和芍药苷的t_1/2分别为（43.34±5.70）,（29.37±2.23）min,MRT分别为（62.54±8.22）,（42.37±3.22）min,AUC_0-t分别为（145 611.50±24 607.85）,（259 667.70±27 544.71）ng·mL^-1·min。结论：不同黄芪剂量组中芒柄花素的MRT及t_1/2均无明显差异。高剂量益气组能延长芍药苷t_1/2、MRT,能延缓芍药苷在体内被代谢,有利于芍药苷在体内维持更持久的作用时间。

Pharmacokinetic study of different dosages of Astragalus membranaceus in Buyang Huanwu Decoction in rats with cerebral ischemic injury by microdialysis combined with LC/MS

OBJECTIVE To explore the pharmacokinetics of the active constituents of Buyang Huanwu Yiqi group and Huoxue group in different doses of Astragalus membranaceus in MCAO rats. METHODS The rat model of cerebral ischemia-reperfusion was copied and the liquid-mass spectrometry method of Buyang Huanwu Decoction was established to study the pharmacokinetic characteristics of active ingredients of the MCAO rats after giving low,medium and high doses (3.09,6.17,12.34 g·kg^-1) of Yiqi group injection and Huoxue group injection (2.32 g·kg^-1). RESULTS The pharmacokinetics of formononetin and paeoniflorin in different administration groups of Buyang Huanwu Decoction accorded with the one-compartment model. The t_1/2 of formononetin and paeoniflorin in low-dose Yiqi group and Huoxue group were respectively (46.89±1.77),(25.47±1.43) min,MRT were (67.66±2.55),(36.74±2.07) min,respectively,AUC_0-t was (39 325.21±7 411.43),(225 496.40±24 990.38) ng·mL^-1·min; medium dose The t_1/2 of formononetin and paeoniflorin in Yiqi group and Huoxue group were (43.73±0.47),(26.24±1.10) min,respectively,and MRT were (63.09±0.68),(37.85±1.59) min,AUC_0-t (67 556.41±7 043.40),(242 206.10±19 296.12) ng·mL^-1·min; t_1/2 of formononetin and paeoniflorin in high-dose Yiqi group and Huoxue group were (43.34±5.70),(29.37±2.23) min,respectively,MRT (62.54±8.22),(42.37±3.22) min,AUC_0-t was (145 611.50±24 607.85),(259 667.70±27 544.71) ng·mL^-1·min,respectively.CONCLUSION There were no significant differences in MRT and t_1/2 between formononetin in different doses of jaundice. The high-dose Yiqi group can prolong paeoniflorin t_1/2 and MRT,which can delay the metabolism of paeoniflorin in the body,which is beneficial to maintain the longer lasting action time of paeoniflorin in the body.