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目的研究葛根素、阿魏酸在局灶性脑缺血模型大鼠体内单用以及合用后的药动学差异,分析2种成分相互影响情况。方法将24只雄性SD大鼠随机分为葛根素组(50 mg/kg)、阿魏酸组(50 mg/kg)以及葛根素与阿魏酸合用组(50 mg/kg+50mg/kg),制备大脑中动脉阻塞(MCAO)模型后,尾iv给药,于不同时间点眼眶取血。应用高效液相色谱仪(HPLC-DAD)测定血浆中葛根素、阿魏酸的质量浓度,应用DAS 3.2.6软件以及SPSS 19.0统计分析软件进行药动学参数的分析处理。结果依据非房室模型的统计矩参数,葛根素单用组、阿魏酸单用组与葛根素与阿魏酸合用组比较,其血药浓度-时间曲线下面积(AUC)、消除半衰期(t1/2)、达峰浓度(Cmax)、一阶矩血浆浓度时间曲线下面积(AUMC)均差异不显著(P>0.05);与葛根素组比较,合用组的葛根素血浆清除率(CL)、平均滞留时间(MRT)差异显著(P<0.05);与阿魏酸组比较,合用组的阿魏酸MRT明显延长(P<0.05)。结论在局灶性脑缺血模型大鼠体内,葛根素与阿魏酸合用能明显延长各自在血液中的MRT,呈现了药物相互作用后的缓释效应。
Objective To study the difference of pharmacokinetics between puerarin and ferulic acid in rats with focal cerebral ischemia after single and combined administration, and analyze the interaction between the two components. Methods Twenty-four male SD rats were randomly divided into puerarin group (50 mg / kg), ferulic acid group (50 mg / kg) and puerarin combined with ferulic acid group (50 mg / kg and 50 mg / , After MCAO model was prepared, caudal iv administration, orbital bleeding at different time points. The plasma concentrations of puerarin and ferulic acid were determined by high performance liquid chromatography (HPLC-DAD). The pharmacokinetic parameters were analyzed by DAS 3.2.6 software and SPSS 19.0 statistical analysis software. Results According to the statistical moment parameter of non-atrioventricular model, the area under the plasma concentration-time curve (AUC) and elimination half-life (p <0.05) were significantly different between the puerarin alone group, the ferulic acid alone group and the puerarin combined with the ferulic acid group (P <0.05). Compared with puerarin group, the plasma clearance rate of puerarin (CL) was significantly lower than that of puerarin group ), Mean residence time (MRT) was significantly different (P <0.05). Compared with the ferulic acid group, the ferulic acid MRT of the combined group was significantly prolonged (P <0.05). Conclusion In the rat model of focal cerebral ischemia, puerarin and ferulic acid can significantly prolong their respective MRTs in the blood, showing a sustained release effect after drug-drug interaction.