在体单向肠灌流模型研究小檗碱及其在复方配伍环境中的大鼠肠吸收特性

本实验主要考察药物浓度、肠段、pH、P-糖蛋白 (P-glycoprotein, P-gp) 及Na⁺依赖型葡萄糖转运体 (Na⁺-dependent glucose transporter, SGLT1) 对小檗碱肠吸收的影响, 并探索复方配伍环境中小檗碱的肠吸收情况。实验以酚红为标示物, 采用大鼠在体单向肠灌流模型, 运用高效液相色谱法考察小檗碱单体 (36.70、46.17和92.33 μg·mL⁻¹)、黄连解毒汤模拟体系 (主要指标成分单体混合物: 小檗碱 + 黄芩苷 + 栀子苷, 其中小檗碱浓度为92.33 μg·mL⁻¹) 及黄连解毒汤全方 (小檗碱浓度为92.33 μg·mL⁻¹) 中小檗碱在大鼠各肠段的吸收变化情况。结果表明: 小檗碱在一定浓度范围内 (20～100 μg·mL⁻¹), 部分大鼠小肠吸收速率参数 (K_a) 无显著性差异, 提示药物的吸收机制可能为被动扩散, 其转运过程可能受SGLT1和P-gp的影响; 单体混合物和全方中小檗碱在各肠段的K_a和有效渗透系数 (P_eff) 值均有显著性增加 (P < 0.05)。说明小檗碱在整个肠段均有吸收, 具有广泛的吸收窗, 其中结肠段吸收较好; 配伍对小檗碱的大鼠肠吸收特性有一定影响, 较单体而言, 单体混合物和全方灌流时小檗碱在小肠中吸收更好。

Intestinal absorption of berberine alone and in combinations by rats single pass intestinal perfusion in situ

The aim of the study is to investigate the effects of concentration, intestinal segments, pH, inhibitors of proteins (P-gp), Na⁺-dependent glucose transporter (SGLT1) on the intestinal absorption of berberine, and to compare intestinal absorption of berberine in combinations.  With phenol red as the indicator, in situ single pass intestinal perfusion (SPIP) model was used and intestinal absorption of pure berberine at concentrations of 36.70, 46.17 and 92.33 μg·mL⁻¹, simulated system of HLJDT (mixture of berberine, baicalin and geniposide), HLJDT with the concentration of berberine 92.33 μg·mL^{−1 in perfusion solution of different intestinal segments (duodenum, jejunum, ileum, and colon) were determined by HPLC in combination with diode array detection} (DAD).  The results indicated that K_a values of berberine at different concentrations had little significant difference among that obtained after perfusing via duodenum, jejunum, ileum and colon indicating that the absorption of berberine was mainly the passive diffusion.  It was also suggested that SGLT1 and P-gp might exert some effects on the absorption of berberine.  K_a and P_eff values of berberine in a mixture of pure compounds and HLJDT for different intestine segments of rat showed an increasing tendency and was significantly different   (P < 0.05) indicating that berberine in a mixture of pure compounds and HLJDT was assimilated better in small intestine.  These results indicate that the intestinal absorption of berberine may be affected by compatibility of compounds.  Additionally, berberine has wide absorption window and better absorption in colon.