大鼠肠管外翻模型对葛根素吸收机制的研究

Study on Absorption Mechanism of Puerarin Using Rat Everted Gut Sac

目的建立准确、灵敏、可靠的葛根素高效液相色谱(HPLC)测定方法,研究葛根素是否存在分肠段吸收的差异并考察肠上皮组织上的p-糖蛋白(P-glycoprotein)对葛根素吸收的影响。方法在不同肠段(空肠、回肠和结肠)的肠管外翻模型中加入葛根素Krebs液,在不同时间点取样并测定囊内药物浓度,比较不同肠段对葛根素通透能力的差异,同时观察p-糖蛋白抑制剂地高辛和维拉帕米对葛根素吸收的影响。结果葛根素在空肠、回肠和结肠的吸收均具有自身浓度抑制作用。随着p-糖蛋白抑制剂地高辛和维拉帕米浓度的增大,葛根素的肠黏膜透过性增强,当浓度分别达到50mg·L-1和200mg·L-1时,这种作用具有一定的饱和性。结论葛根素在各肠段的吸收有可能存在主动转运的过程,葛根素是p-糖蛋白的底物。

Objective To develop an accurate, sensitive and reliable HPLC method for puerarin, and to study the absorption characteristics of puerarin in different intestinal sections （jejunum, ileum and colon） and the influence of p -glycoprotein on the absorption rate. Methods Rat everted gut sac was used. Sac containing drug free Krebs solution was immersed into the Krebs solution containing puerarin. The solution inside the sac was collected and drug concentration was determined by HPLC method. Digoxin and verapamil were used to study the influence of p - glycoprotein on the absorption of puerarin. Results With an increase of the concentration of puerarin, puerarin absorption across intestinal membrane was increased in the rat jejunum, ileum and colon, but there exited a saturable transport process for puerarin. With an increase of the concentration of verapamil and digoxin, puerarin absorption across intestinal membrane increased in the rat jejunum, ileum and colon, but when the concentration of digoxin and verapamil was 50 and 200 mg·L^-1, the increase had a saturable process. Conclusion The absorption of puerarin across intestinal sac may be an active transportation mediated by p -glycoprotein transporter.