羟基红花黄色素A的Caco-2细胞摄取转运研究

 目的研究羟基红花黄色素A(HSYA)的胃肠吸收转运机制。方法采用Caco-2细胞模型考察孵育时间、介质pH、药物浓度及抑制剂(环孢菌素A和叠氮钠)对羟基红花黄色素A摄取转运的影响,并分析HSYA灌胃给药后在大鼠尿及粪中的累积排泄。结果HSYA的摄取符合被动扩散过程,pH7.8环境下药物的细胞摄取量(1.05±0.045)mg·g^-1]低于pH5.4(1.24±0.09)mg·g^-1](P<0.05),其在Caco-2单细胞层的表观透过系数(Papp)为(2.16±1.21)×10^-8cm·s^-1,加入环孢菌素A和叠氮钠后其Papp显著提高(P<0.05),分别为(47.92±17.8)×10^-8和(12.53±4.55)×10^-8cm·s^-1。HSYA大鼠灌胃给药(5.6mg·kg^-1)后31h,其尿和粪中的累积排泄量分别为给药剂量的0.74%和28.57%。结论HSYA的吸收基本符合被动扩散过程并有P-gp的参与,其黏膜透过性较差,碱性环境相对不利于药物的吸收。HSYA口服后的胃肠吸收较差,大量的药物被排出体外或在胃肠道内被代谢转化。

Uptake and Transport of Hydroxysafflor Yellow A in Caco-2 Cells Monolayer

OBJECTIVE To study the absorption mechanism of hydroxysafflor yellow A(HSYA) in gastrointestinal(GI) tract.METHODS Caco-2 cells monolayer was employed to investigate the effect of incubation time,pH of circumstance,drug concentration and inhibitors(cyclosporine A and NaN3) on HSYA uptake(or transport),and excretion experiments of HSYA in rats after intragastric administration was further conducted.RESULTS Uptake of HSYA in Caco-2 cells monolayer rising linearly with increasing concentration indicated a passive diffusion.Decreased uptake (1.05±0.045) mg·g^-1] of HSYA in Caco-2 cells was observed at pH 7.8 comparing to that at pH 5.4 (1.24±0.09) mg·g^-1].The apparent permeability coefficient of(2.16±1.21)×10^-8cm·s^-1 for HSYA(1 g·L^-1) in Caco-2 cells monolayer was increased dramatically to(47.92±17.8)×10^-8 and(12.53±4.55)×10^-8cm·s^-1 by cyclosporin A and NaN₃,respectively.Accumulative excretion of HSYA in urine and feces were 0.74% and 28.57% respectively after intragastric administration(5.6 mg·kg^-1) in rats for 31 h.CONCLUSION Absorption process of HSYA in Caco-2 cells monolayer met the characteristics of passive diffusion and the efflux caused by P-gp was also involved.The membrane permeability of HSYA is extremely low and alkaline circumstance is disadvantageous for the HSYA absorption.The absorption of HSYA in GI tract is little and much more HSYA are excreted in feces or transformed by the metabolism enzymes in GI tract.