辣椒素对P-糖蛋白和细胞旁途经转运透过的作用  

Effect of capsaicin on intestinal permeation of P-glycoprotein substrate rhodamine 123 and fluorescein sodium in rats

作　　者：梁倩莹 段炼[2] 庄志铨[3] 赵博欣[1] 刘媛[1] 王胜奇[1] 杨富恒 刘思佳[1] 李国锋[1] 

机构地区：[1]南方医科大学南方医院,广东广州510515 [2]广州医科大学第二附属医院,广东广州510260 [3]广东药学院附属第一医院,广东广州510080

出　　处：《南方医科大学学报》2015年第5期724-727,732,共5页Journal of Southern Medical University

基　　金：国家自然科学基金(81173014);广东省科技计划项目(2010B030700014);南方医院院长基金(2010B015)~~

摘　　要：目的通过研究P-糖蛋白(P-gp)底物罗丹明123(R123)在空肠、回肠和结肠转运时辣椒素的作用,探究辣椒素对肠粘膜上P-gp功能的影响。方法使用体外扩散池法技术,分别取SD雄性大鼠的空肠、回肠和结肠肠段标本,计算各肠段中吸收方向(mucosa to serosa,M-S)和分泌方向(serosa to mucosa,S-M)R123的表观渗透速率(Papp)。用荧光分光光度计测定R123和荧光素钠(CF)在接收室中的浓度。结果在辣椒素作用下,R123经空肠粘膜透过时,吸收方向与空白组相比显著增高,分泌方向显著降低,但其在回肠及结肠M-S组及S-M组表观渗透系数Papp与空白组相比均没有显著性差异。CF经空肠粘膜透过时,MS组及S-M组Papp与空白组相比均显著增高;经回肠和结肠粘膜透过与空白组相比没有显著性差异。结论辣椒素影响P-gp底物R123和细胞旁转运药物CF经肠粘膜透过的作用具有肠段差异性,对R123和CF的影响仅存在于空肠,表明辣椒素是一种较弱的P-gp抑制剂和粘膜通道改善剂。可能与P-gp和紧密连接在肠粘膜上的逐渐变化的分布有关。Objective To investigate the role of capsaicin in regulating permeation of P-gp substrate rhodamine 123 （R123） across the jejunum, ileum and colon membranes of rats. Methods The permeability of R123 or fluorescein sodium （CF） across the jejunum, ileum and colon membranes of male SD rats was evaluated using a Ussing chamber. The concentration of R123 or CF in the receptor was determined using fluorospectrophotometry to calculate the apparent permeability coefficient （Papp）. Results Compared with the blank control group, capsaicin increased the permeability of R123 across jejunal membranes in the mucosal-to-serosal （M-S） direction and decreased its permeability in the serosal-to-mucosal （S-M） direction, but produced no obvious effect on R123 transport across the ileum or colon membranes. Capsaicin caused a regional increase in the permeability of CF across the jejunal membranes compared with the control group, but CF transport across the ileum and colon membranes was not affected. Conclusion Capsaicin can affect the transport of R123 and CF across rat jejunal membranes, and this effect is shows an obvious intestine segment-related difference probably because of the different distribution of P-gp or tight junction in the intestines. This finding suggests that capsaicin is a weak P-gp inhibitor and an improver of mucous membrane channels.

关 键 词：辣椒素 P-糖蛋白 罗丹明123 肠粘膜 细胞旁途径 

分 类 号：R3411[医药卫生—基础医学]