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目的研究降血压肽Val-Leu-Pro-Val-Pro(VLPVP)在Caco-2细胞模型中的吸收机制。方法用体外培养的Caco-2细胞单层模型,考察时间、pH值、药物浓度、吸收抑制剂及促进剂对VLPVP吸收的影响。用HPLC法检测VLPVP的浓度。结果VLPVP在pH7.4时转运量最大,且与浓度和时间呈正相关。肽转运载体竞争性抑制剂Gly-Pro、arphamenine A和细胞内吞抑制剂氧化苯胂对VLPVP的转运没有显著的抑制作用,而旁路转运促进剂去氧胆酸钠、多药耐药蛋白抑制剂MK-571和能量抑制剂叠氮化钠对VLPVP从AP侧至BL侧的转运有非常显著的促进作用,而叠氮化钠和MK-571对VLPVP从BL侧至AP侧的转运无显著影响。结论VLPVP以旁路转运为主要方式被小肠上皮细胞吸收,并受到多药耐药蛋白MRP2强烈的外排作用。
Objective To study the mechanism of the up-regulation of Val-Leu-Pro-Val-Pro (VLPVP) in Caco-2 cell model. Methods Caco-2 cell monolayers were cultured in vitro, and the effects of time, pH value, drug concentration, absorption inhibitors and accelerators on the uptake of VLPVP were investigated. The concentration of VLPVP was determined by HPLC. Results VLPVP had the highest translocation at pH7.4 and positive correlation with concentration and time. Peptide transporter competitive inhibitors Gly-Pro, arphamenine A and the endocytosis inhibitor phenylarsenazon did not significantly inhibit the transport of VLPVP, while the bypass transporter sodium deoxycholate, multidrug resistance protein inhibition The agent MK-571 and the energy inhibitor sodium azide had a very significant promoting effect on the transport of VLPVP from the AP side to the BL side, whereas sodium azide and MK-571 had no significant transport of VLPVP from the BL side to the AP side influences. Conclusion VLPVP is mainly absorbed by the small intestine epithelial cells in a bypass manner and is strongly effluxed by multidrug resistance protein MRP2.