Abstract：
Some glycoside drugs can be transported through intestinal glucose transporters (IGTs). The surfactants used in oral drug preparations can affect the function of transporter proteins. This study aimed to investigate the effect of commonly used surfactants, Poloxamer 188 and Tween 80, on the drug transport capacity of IGTs. Previous studies have shown that gastrodin is the optimal drug substrate for IGTs. Gastrodin was used as a probe drug to evaluate the effect of these two surfactants on intestinal absorption in SD rats through pharmacokinetic and in situ single-pass intestinal perfusion. Then, the effects of the two surfactants on the expression of glucose transporters and tight-junction proteins were examined using RT-PCR and western blotting. Additionally, the effect of surfactants on intestinal permeability was evaluated through hematoxylin-eosin staining. The results found that all experimental for Poloxamer 188 (0.5%, 2.0% and 8.0%) and Tween 80 (0.1% and 2.0%) were not significantly different from those of the blank group. However, the AUC(0-∞) of gastrodin increased by approximately 32% when 0.5% Tween 80 was used. The changes in IGT expression correlated with the intestinal absorption of gastrodin. A significant increase in the expression of IGTs was observed at 0.5% Tween 80. In conclusion, Poloxamer 188 had minimal effect on the drug transport capacity of IGTs within the recommended limits of use. However, the expression of IGTs increased in response to 0.5% Tween 80, which significantly enhanced the drug transport capacity of IGTs. However, 0.1% and 2.0% Tween 80 had no significant effect.
摘要：
一些糖苷药物可以通过肠道葡萄糖转运蛋白(IGT)转运。口服药物制剂中使用的表面活性剂可以影响转运蛋白的功能。本研究旨在探讨常用表面活性剂的作用,泊洛沙姆188和吐温80，对IGTs的药物转运能力的影响。先前的研究表明天麻素是IGT的最佳药物底物。以天麻素作为探针药物，通过药代动力学和原位单次灌肠评价这两种表面活性剂对SD大鼠肠道吸收的影响。然后，使用RT-PCR和蛋白质印迹法检查了两种表面活性剂对葡萄糖转运蛋白和紧密连接蛋白表达的影响。此外,通过苏木精-伊红染色评价表面活性剂对肠道通透性的影响.结果发现,所有实验为泊洛沙姆188(0.5%,2.0％和8.0％）和Tween80（0.1％和2.0％）与空白组没有显着差异。然而,当使用0.5%吐温80时,天麻素的AUC(0-∞)增加约32%。IGT表达的变化与天麻素的肠道吸收有关。在0.5%Tween80时观察到IGT的表达显著增加。总之,泊洛沙姆188在推荐的使用范围内对IGT的药物转运能力影响最小。然而,0.5%吐温80后,IGTs的表达增加,显著增强了IGTs的药物转运能力。然而,0.1%和2.0%吐温80均无显著影响。
