目的 研究穿心莲提取物中穿心莲内酯和脱水穿心莲内酯的大鼠在体肠吸收特性。方法 采用大鼠在体肠灌注实验模型,以紫外分光光度法测定酚红质量浓度,高效液相色谱法测定灌注液中穿心莲内酯和脱水穿心莲内酯质量浓度,分别研究质量浓度、pH值和吸收部位对穿心莲内酯和脱水穿心莲内酯肠吸收的影响。结果 随着穿心莲提取物(111.22～335.78 μg/mL)质量浓度的增加,穿心莲内酯的吸收速率常数(K_a)和单位时间吸收率(P)均降低;随着pH值由5.34升至6.38,穿心莲内酯的K_a和P略微增加,随着pH值由6.38升至7.40,穿心莲内酯的K_a和P均降低;穿心莲内酯在不同肠段中均有吸收,各肠段的P按十二指肠、空肠、回肠、结肠顺序依次下降。穿心莲提取物在111.22～222.78 μg/mL随着质量浓度增大,脱水穿心莲内酯的K_a和P均下降;穿心莲提取物在222.78～335.78 μg/mL随着质量浓度增大,脱水穿心莲内酯的K_a和P基本无变化;pH值5.34时吸收较好,随着pH值由5.34升至7.40,脱水穿心莲内酯的K_a和P呈略微下降的趋势;P按回肠、空肠、结肠、十二指肠顺序依次下降。结论 穿心莲提取物中穿心莲内酯和脱水穿心莲内酯在小肠的吸收均不是简单的被动扩散,还包括载体媒介转运;吸收均受pH值的影响;十二指肠为穿心莲内酯的最佳吸收部位,回肠为脱水穿心莲内酯的最佳吸收部位;肠吸收时穿心莲提取物中其他成分对穿心莲内酯的吸收基本无影响,但对脱水穿心莲内酯的吸收有一定的促进作用。

Objective To investigate the intestinal absorptive characteristics of andrographolide (A) and dehydroandrographolide (DDA) in the extract of Andrographis paniculata in rats. Methods The intestine of rat was cannulated for in situ perfusion. UV was used to determine the concentration of phenol red, and HPLC was used to determine the concentration of A and DDA. The effects of drug concentration, pH value, and absorption site on the absorption had been studied. Results In 111.22-335.78 μg/mL dose range of A. paniculata extract, K_a and P of A were reduced with the increase of concentration. With the pH value increasing from 5.34 to 6.38, K_a and P were increased slightly. With the pH value increasing from 6.38 to 7.40, K_a and P had a downward trend. A was absorbed in various sections of intestines, and the P descended in the order of duodenum, jejunum, ileum, and colon. In 111.22-222.78 μg/mL dose range of A. paniculata extract, K_a and P were reduced with the increase of concentration. In 222.78-335.78 μg/mL dose range, K_a and P had no change with the increase of concentration. Under the condition of pH 5.34, the absorption was better. With the pH value increasing from 5.34 to 7.40, K_a and P showed a slight downward trend, and P descended in the order of ileum, jejunum, colon, and duodenum. Conclusion The intestinal absorption mechanism of A and DDA in A. paniculata extract is not just passive transport, but also including the carrier medium transport which are both affected by pH value. The best absorption site of A is duodenal, and the best absorption site of DDA is ileumother. Other components may have no significant influence to the intestinal absorption of A, but they may promote the intestinal absorption of DDA.

国家自然科学基金资助项目(81373974);河南省科技厅重点科技攻关项目(122102310029)