原儿茶醛与羟基红花黄色素A单用与合用在高脂血症大鼠体内的药动学-药效学相关性研究

探讨原儿茶醛以及羟基红花黄色素A单用与合用在高脂血症大鼠体内的药动学及药效学相关性研究。该实验建立高脂血症大鼠模型,尾静脉注射液原儿茶醛(20 mg·kg~(-1))及羟基红花黄色素A(12 mg·kg~(-1)),采用HPLC-DAD测定不同时间内原儿茶醛和羟基红花黄色素A的血药浓度,并绘制药-时曲线;同时测定各时间点血浆中血小板活化因子(PAF),血浆a颗粒膜蛋白(GMP-140)含量,绘制时间-效应曲线;采用DAS 3.2.6软件处理并进行相关性分析,比较分析单用及合用后原儿茶醛与羟基红花黄色素A在模型大鼠体内的药动学差异以及药效学指标的变化,评价原儿茶醛、羟基红花黄色素A在高脂血症大鼠体内的影响作用。结果原儿茶醛、羟基红花黄色素A在高脂血症大鼠体内单用及合用后,均符合三房室模型,模型组血浆中PAF及GMP-140明显升高,给予药物后在一定时间内降低PAF及GMP-140在体内的含量。原儿茶醛与羟基红花黄色素A抗药效指标的作用可能与其在体内的水平高低有关,并且其血药浓度与血浆中PAF及GMP-140的含量呈正相关。在高脂血症大鼠体内原儿茶醛和羟基红花黄色素A具有一定的互为影响作用,并且合用后药效学指标更好,同时也反映了原儿茶醛、羟基红花黄色素A合用在临床用药的合理性。

Pharmacokinetics-pharmacodynamics correlation of protocatechuic aldehyde and hydroxysafflor yellow A alone or their combination use in rats with hyperlipidemia

To study the pharmacokinetics-pharmacodynamics correlation of protocatechuic aldehyde and hydroxysafflor yellow A alone or their combination use in rats with hyperlipidemia. In this study, the hyperlipidemia model was established by intravenous injection of protocatechuic aldehyde (20 mg·kg^-1) and hydroxysafflor yellow A (12 mg·kg^-1). The HPLC-DAD method was applied to determine the plasma concentration of protocatechuic aldehyde and hydroxysafflor yellow A at different time points and draw the drug effect-time curve. Meanwhile, the platelet activating factors (PAF) and plasma a granule membrane protein (GMP-140) contents were determined at different time points to draw the time-effect curve. Then DAS 3.2.6 software was used to process the data, analyze their correlation, and compare the difference of pharmacokinetics and pharmacodynamics of protocatechuic aldehyde and hydroxysafflor yellow A in hyperlipidemia rats after alone or their combined application, so as to evaluate the effect of protocatechuic aldehyde and hydroxysafflor yellow A on hyperlipidemia rats. According to the result, the pharmacokinetics and pharmacodynamics process of protocatechuic aldehyde and hydroxysafflor yellow A in hyperlipidemia rats after alone or their combination were consistent to the three-compartment model. In model group, the plasma PAF and GMP-140 were significantly increased, and the PAF and GMP-140 in vivo contents were decreased in a certain time after treatment. The effects of protocatechuic aldehyde and hydroxysafflor yellow A against the pharmacodynamic action may be related with their level in vivo, and their plasma concentration was positively related to the PAF and GMP-140 contents. The pharmacodynamic indexes were better after the combined use of protocatechuic aldehyde and hydroxysafflor yellow A, with certain influence on each other in hyperlipidemia rats; at the same time, it also reflected the rationality of protocatechuic aldehyde and hydroxysafflor yellow A combined application.