基于Caco-2细胞单层与大鼠小肠模型的大豆皂苷Ⅰ和Ⅱ经上皮传递的变化研究(英文)

Variability of Transepithelial Transport of Soyasaponins Ⅰ and Ⅱ Using a Caco-2 Cell Monolayer and a Rat Intestinal Model

利用Caco-2细胞单层与大鼠小肠模型研究大豆皂苷Ⅰ和Ⅱ的吸收变化与机制。在Caco-2细胞单层中,大豆皂苷Ⅰ和Ⅱ从肠腔侧到基底侧的表观渗透系数(apparent permeability coefficients,Papp)随时间的延长趋向平稳,前120 min近似线性,且随浓度增大,斜率减小,Papp值分别为(1.02×10-6~3.41×10-6)cm/s和(0.9×10-6~3.05×10-6)cm/s;传递的饱和性、双侧Papp比率>1.5以及线粒体呼吸链抑制剂叠氮化钠的抑制作用表明了两者的主动转运机制。抑制剂维拉帕米没有提高大豆皂苷Ⅰ和Ⅱ的吸收,排除了p-糖蛋白介导的外排;吸收促进剂按照冰片>脱氧胆酸钠>卡波姆934P>聚山梨酯80的强弱提高两者的吸收,壳聚糖则未能加强渗透。跨膜转运也表现出组织差异性:两者在大鼠空肠的Papp是十二指肠和回肠的2倍多。因此,控制的传递应能提高大豆皂苷Ⅰ和Ⅱ的小肠吸收以便两者实施它们的生理功能。

The absorption mechanism and variability of soyasaponins I and II were investigated using a Caco-2 cell monolayer and a rat intestinal model. Apparent permeability coefficients(Papp) across the Caco-2 model increased linearly until plateaus were reached at 120 min with intermediate Papp values of(1.02-3.41) × 10^(-6) and(0.9-3.05) × 10^(-6) cm/s for two soyasaponins, respectively. Saturable transport, bilateral Papp ratios of more than 1.5 and the inhibitory effect of mitochondrial electron transport chain blocker sodium azide indicated the active transport mechanisms. The transmembrane permeability glycoprotein(p-glycoprotein) inhibitor verapamil did not increase the permeation of both soyasaponins, excluding the p-glycoprotein-related efflux. Several absorption enhancers promoted the permeation across the Caco-2 cell monolayers with a rank of borneol > sodiumdeoxycholate > carbomer 934 P polysorbate 80; but chitosan did not exhibit such an enhancing ability. The transepithelial transport also showed tissue difference in the intestine with the P_(app) values for soyasaponins I and II across the jejunal segment being more than 2 times greater than those across the duodenal and ileal segments. Therefore, a controlled transport should be able to improve the intestinal absorption so that soyasaponins I and II would exert their health functions.