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对基于P-糖蛋白(P-gp)肠吸收单灌流模型进行验证。首先,通过酚红灌流,采用质量法进行水分校正,通过高效液相色谱法对灌流前后酚红水平进行检测,以验证肠上皮细胞的紧密连接结构正常,且肠上皮的完整性保持良好;其次,采用FDA指定阳性药地高辛对模型进行验证,给予大鼠不同质量浓度维拉帕米后,对大鼠回肠段地高辛吸收参数进行观察对比。酚红在大鼠体内回肠段存在吸收,吸收参数有效渗透系数Peff为(1.09±0.62)×10~(-6)cm·s~(-1),结果表明肠上皮细胞的紧密连接结构正常,且肠上皮的完整性保持良好,地高辛灌流不给予维拉帕米时,地高辛在回肠段存在一定程度的吸收,吸收参数有效渗透系数Peff为(1.07±0.59)×10~(-5)cm·s~(-1),给予大鼠0.01,0.1 mmol·L~(-1)浓度的维拉帕米后,地高辛在大鼠回肠的吸收呈上升趋势,吸收参数有效渗透系数Peff分别为(1.58±0.69)×10~(-5),(3.28±0.95)×10-5cm·s~(-1),高浓度时,数据差异具有统计学意义(P<0.05)。地高辛灌流实验验证了小肠上皮P-gp表达完整,可以用于P-gp外排转运体的研究。
A single-pass perfusion model based on P-glycoprotein (P-gp) intestinal absorption was validated. First of all, phenol red perfusion, the use of mass method for water correction, high performance liquid chromatography before and after phenolphthalein level was tested in order to verify the tight junction of intestinal epithelial cells normal structure, and the integrity of the intestinal epithelial well maintained; followed by , The positive drug designated by the FDA digoxin model to verify the different concentrations of verapamil given rat after ileum digoxin absorption parameters were observed and compared. Phenol red showed absorption in the ileum of rats, and the effective permeability coefficient (Peff) of absorption parameters was (1.09 ± 0.62) × 10 -6 cm · s -1. The results showed that the tight junctions of intestinal epithelial cells were normal, And the integrity of intestinal epithelium was maintained well. When digalum was not given by digoxin infusion, digoxin showed some degree of absorption in the ileum. The effective permeability coefficient (Peff) of absorption parameters was (1.07 ± 0.59) × 10 ~ (- 5) cm · s ~ (-1), the absorption of digoxigenin in the ileum of rats increased after 0.01,0.1 mmol·L -1 of verapamil was administered to rats, and the absorption parameters were effectively permeated The coefficients of Peff were (1.58 ± 0.69) × 10 -5 and (3.28 ± 0.95) × 10-5cm · s -1, respectively. There was a significant difference in data between the two groups (P <0.05). Digoxigenin perfusion experiments confirmed the integrity of P-gp expression in intestinal epithelium and could be used for the study of P-gp efflux transporter.