论文部分内容阅读
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。
Objective To study the gastrointestinal absorption and transport mechanism of hydroxysafflor yellow A (HSYA). Methods Caco-2 cell model was used to investigate the effects of incubation time, pH, drug concentration and inhibitors (cyclosporin A and sodium azide) on uptake and transport of hydroxysafflor yellow A Cumulative excretion in rat urine and faeces. Results The uptake of HSYA was in accordance with the passive diffusion process. The cellular uptake of HSG was lower than that of pH 5.4 [(1.05 ± 0.045) mg · g -1] at pH7.8 [(1.24 ± 0.09) mg · g -1] <0.05). The apparent Papp of Caco-2 monolayer was (2.16 ± 1.21) × 10-8cm · s-1. The addition of cyclosporine A and sodium azide increased Papp significantly (P <0.05), which were (47.92 ± 17.8) × 10-8 and (12.53 ± 4.55) × 10-8cm · s-1, respectively. The cumulative excretion of urinary and excretion in HSYA rats was 0.74% and 28.57%, respectively, 31 h after intragastric administration (5.6 mg · kg -1). Conclusions The absorption of HSYA is basically consistent with the passive diffusion process and P-gp is involved. The permeability of HSYA is poor, and the alkaline environment is not conducive to the absorption of drugs. HSYA after oral administration of gastrointestinal absorption is poor, a large number of drugs are excreted or in the gastrointestinal tract was metabolic transformation.