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药动学―药效学相关性研究.docVIP

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药动学―药效学相关性研究 　　[摘要] 探?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。 　　[关键词] 原儿茶醛；羟基红花黄色素A；高脂血症模型；药动学；药效学；联合用药 　　[Abstract] 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-1