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(t_1/2)、达峰浓度(C_max)、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 pharmacokinetic changes of puerarin and ferulic acid alone or their combination used in rats with focal cerebral ischemia and to analyze their mutual influence. Methods Twenty-four SD rats were randomly divided into three groups such as puerarin (50 mg/kg) group, ferulic acid (50 mg/kg) group, and combination (50 mg/kg + 50 mg/kg) group. The middle cerebral artery occlusion (MCAO) model was established. The model rats were iv injected with puerarin and ferulic alone, and then the blood was collected at different time points. The HPLC-DAD method was applied to determining the plasma concentration of puerarin and ferulic acid at different time points and the drug-time curve was drawn. The DAS 3.2.6 and SPSS 19.0 softwares were used to analyze the data. Results The pharmacokinetic parameters: AUC, t_1/2, C_max, and AUMC had no significant difference (P > 0.05), while the clearance of puerarin group had the significant difference with that of the combination group and mean residence time (MRT) of combination group was more extended than that of ferulic acid group. Conclusion In rats with focal cerebral ischemia, the combination of puerarin and ferulic acid could significantly extend the MRT in rats, which reflects the slow-release effect between drug-drug interaction.

国家自然科学基金资助项目(81374053,81274176,81202636);浙江省中医药(中西医结合)重点学科(2012-XK-A06)