利用Caco-2细胞模型研究白鲜碱和茵芋碱在人小肠的吸收  

Absorption of dictamnine and skimmianine across human intestinal epithelial in a model of Caco-2 cell monolayers

作　　者：马莲[1] 王莹[1] 杨秀伟[1] 

机构地区：[1]北京大学药学院天然药物学系天然药物及仿生药物国家重点实验室,北京100083

出　　处：《中国新药杂志》2008年第2期124-128,共5页Chinese Journal of New Drugs

基　　金：北京大学"十五211工程";国家高技术领域研究"863"计划(2002AA2Z343C);北京市科委科技专项(Z0004105040311);天然药物及仿生药物国家重点实验室开放课题资助项目

摘　　要：目的:研究中药化学成分白鲜碱和茵芋碱的人小肠吸收情况。方法:利用人源结肠腺癌细胞系Caco-2细胞单层模型观察白鲜碱和茵芋碱由绒毛面(AP端)到基底面(BL端)、BL端到AP端2个方向的转运过程。应用偶联紫外检测器的高效液相色谱法对上述2种生物碱进行定量分析,计算转运参数和表观渗透系数,并与阳性对照药普萘洛尔和阿替洛尔进行比较。结果:由AP端到BL端,白鲜碱和茵芋碱的表观渗透系数(Papp)分别为(1.59±0.14)×10-5cm.s-1和(3.19±0.09)×10-5cm.s-1;由BL端到AP端,白鲜碱和茵芋碱的Papp分别为(2.57±0.33)×10-5cm.s-1和(5.86±0.49)×10-5cm.s-1,与在Caco-2单层细胞模型上呈良好吸收的阳性对照药普萘洛尔的基本一致。结论:白鲜碱和茵芋碱可以通过小肠上皮细胞被动吸收进入体内,属于吸收良好的化合物。Objective： To study the absorption of dictamnine and skimmianine, the constituents of traditional Chinese medicines, in human intestinal epithelial. Methods： Caco-2 （the human colon adenocarcinoma cell lines） cell monolayers were used as an intestinal epithelial cell model. The permeability of dictamnine and skimmianine from apical side （AP side） to basolateral side （ BL side） or from BL side to AP side were observed. The concentrations of the two compounds were measured by high performance liquid chromatography （HPLC） coupled with UV detector. Transport parameters and permeability coefficients （Papp） were then calculated, and Papp values were compared with the reported values for model compounds, propranolol and mannitol. Results： The Papp values of dictamnine and skimmianine were （1.59±0.14） ×10^-5cm·s^-1 and （3.19 ±0.09）×10^-5cm·s^-1 from AP side to BL side, and （2.57 ±0.33） ×10^-5cm·s^-1and （5.86 ±0.49）×10^-5cm·s^-1 from BL side to AP side, respectively. Their Papp values were identical with those of propranolol, which is a transcellular transport marker and used as a control substance for high permeability with a Papp value of ≥ 1.0 ×10^-5cm·s^-1 Conclusion： Dictamnine and skimmianine can be absorbed across intestinal epithelial cells, and both of them are completely absorbed compounds.

关 键 词：CACO-2细胞单层 白鲜碱 茵芋碱 肠吸收 表观渗透系数 

分 类 号：R329.25[医药卫生—人体解剖和组织胚胎学] R333.3[医药卫生—基础医学]