苦参碱大鼠肠吸收动力学研究

Intestinal absorption kinetics of matrine in rats

目的对苦参碱大鼠肠吸收进行考察并探讨P-糖蛋白(P-glycoprotein,P-gp)和有机阳离子转运蛋白(OCTs)在其吸收中的作用。方法采用大鼠在体单向肠灌流结合HPLC法,考察苦参碱在不同肠段的吸收状况及不同浓度苦参碱的肠吸收情况,同时采用P-gp和OCTs抑制剂对两种转运蛋白抑制后,考察大鼠空肠对苦参碱吸收的影响,从而初步探讨P-gp和OCTs对苦参碱肠吸收的影响。结果苦参碱(400μg/mL)在十二指肠、空肠、回肠、结肠的吸收速率常数分别为0.25×10-2、0.80×10-2、0.40×10-2、0.35×10-2/min;不同质量浓度苦参碱(100、200、400μg/mL)的吸收速率常数(Ka)分别为:0.79×10-2、0.81×10-2、0.80×10-2/min。在维拉帕米、西咪替丁存在下,苦参碱(400μg/mL)的表观吸收系数(Papp)值分别为0.86×10-3、0.80×10-3/min。结论苦参碱在各肠段都有吸收,其中在空肠吸收最好,其吸收机制可能为被动吸收,苦参碱可能不是P-gp和OCTs的底物。

AIM To explore the intestinal absorption of matrine,the effects of P-gp and organic cation transporters（OCTs） on its intestinal absorption in rats.METHODS The absorption of matrine in different intestinal segments and three concentrations of matrine（100,200,and 400 μg/mL） were studied by in situ rats single pass perfusion model combined with HPLC.The influence of P-gp inhibitor（verapamil） and OCTs inhibitor（cimetidine） on the absorption of matrine were also investigated.RESULTS The Ka of matrine was 0.80×10-2,0.40×10-2,0.35×10-2,and 0.25×10-2/min for jejunum,ileum,colon and duodenum,respectively.The Ka value had no significant difference between the different concentrations of matrine in jejunum,and the value of Ka was 0.79×10-2,0.81×10-2,and 0.80×10-2/min for 100,200,400 μg/mL matrine,respectively.With the presence of verapamil or cimetidine,the Papp of matrine（400 μg/mL） was 0.86×10-3 and 0.80×10-3/min,respectively.CONCLUSION The results indicate that the absorption of matrine is passive diffusion.Compared with the other segments,the main site of uptake of matrine appears to be located in the jejunal compartment of the rat gut.Matrine may not be a substrate of P-gp and OCTs.