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目的研究千金子甾醇在大鼠肠道内的吸收情况以及P-糖蛋白(P-gp)和多药耐药相关蛋白(MRP2)对千金子甾醇肠吸收的影响。方法采用大鼠在体单向肠灌流模型,运用高效液相色谱法测定十二指肠、空肠、回肠、结肠灌流液中千金子甾醇的含量,计算吸收速率常数(Ka)和表观渗透系数(Papp)。结果千金子甾醇在大鼠结肠的Ka及Papp最高(P<0.05)。加入P-gp抑制剂盐酸维拉帕米后,千金子甾醇在结肠段的Ka及Papp显著增加;而加入MRP2抑制剂吲哚美辛后,千金子甾醇在大鼠结肠段的Ka及Papp普遍降低。结论千金子甾醇在肠道中的主要吸收部位为结肠,推测千金子甾醇可能为P-gp的底物,而非MRP2的底物。
Objective To study the absorption of sesto sterol in rat intestine and the effects of P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP2) on intestinal steroid absorption. Methods The rat model of single intestinal perfused rat was established. The content of trichostatin in duodenum, jejunum, ileum and colon perfusate was determined by high performance liquid chromatography. The absorption rate constant (Ka) and apparent permeability coefficient (Papp). Results Serum sterol had the highest Ka and Papp in the rat colon (P <0.05). After addition of P-gp inhibitor verapamil, the levels of Ka and Papp in the colonic segment increased significantly. However, the addition of MRP2 inhibitor indomethacin resulted in the widespread sequestration of Ka and Papp in the colon of rats reduce. Conclusions The main absorption site of trichostatin in the intestine is colon, suggesting that trichostatin may be the substrate of P-gp rather than the substrate of MRP2.