青娥丸方有效成分药动学药效学相关性研究.docVIP

青娥丸方有效成分药动学药效学相关性研究 　　[摘要]研究青娥丸方中3?N有效成分京尼平苷酸、补骨脂素、异补骨脂素在大鼠体内的药代动力学过程与其抗骨质疏松作用的相关性。该实验通过大鼠灌胃给药青娥丸生品与盐炙品后，选取不同时间点进行眼眶取血，采用UHPLCMS/MS测定大鼠血浆中京尼平苷酸、补骨脂素和异补骨脂素的药物浓度，绘制药时曲线；以成骨细胞的增殖率为药效学指标，采用MTT法测定不同时间点含药血清作用于成骨细胞后的增殖率，绘制时效曲线。比较时效曲线和药时曲线可以发现，在成骨细胞的增殖率达到峰值时，京尼平苷酸和补骨脂素的血药浓度也在峰值附近，表明两者具有较好的相关性。而异补骨脂素的血药浓度峰值相对于药效峰值具有一定的滞后性。将青娥丸生品及盐炙品各成分的时效曲线与药时曲线进行拟合，进行相关性分析，发现盐炙品组各成分的相关性略高于生品组。上述实验结果表明，青娥丸中京尼平苷酸、补骨脂素的药时曲线和时效曲线具有良好的相关性，且与生品相比，青娥丸盐炙品中两者的相关性更高。 　　[关键词]青娥丸； 药动学； 药效学； 京尼平苷酸； 补骨脂素； 异补骨脂素 　　Analysis on pharmacokineticspharmacodynamics correlation of 　　effective ingredients of Qing′e wan 　　LIU Ling1，2， WENG Zebin3， WANG Heng1，2， ZHU Xingyu1，2， CHEN Zhipeng1，2， WU Li1，2， LI Weidong1，2* 　　（1 Jiangsu Key Laboratory of Chinese Medicine Processing， Nanjing University of Chinese Medicine， Engineering Center 　　for Standardization of Traditional Chinese Medicine Processing under State Ministry of Education， Nanjing 210046， China； 　　2 Pharmacy College of Nanjing University of Chinese Medicine， Nanjing 210046， China； 　　3 China Pharmaceutical University， Nanjing 210009， China） 　　[Abstract]To study the pharmacokinetics of three active ingredients in Qing′e wan， namely geniposidic acid， psoralen and isopsoralen， in rats， in order to investigate their correlation in the antiosteoporotic effect The rats were taken blood from their eye sockets at different time points after being orally administered with raw and saltprocessed Qing′e wan Geniposidic acid， psoralen and isopsoralen in rats plasma were determined by means of UHPLCMS/MS to draw the concentrationtime curve The proliferation rate of osteoblasts was taken as the pharmacodynamic index， and determined by MTT method to draw effecttime curve In comparison between the effecttime curve and the concentrationtime curve， the blood concentrations of geniposidic acid and psoralen were close to the peak when the cell proliferation rate reached its peak， indicating a good correlation between them The peak blood concentration of isopsoralen wa