Rubas W, Jezyk N, Grass G M
Department of Pharmaceutical Sciences, Syntex Research, Palo Alto, CA 94303, USA.
J Drug Target. 1995;3(1):15-21. doi: 10.3109/10611869509015928.
The in vitro permeabilities of 14C labeled dextrans (10, 40, and 70 kD) were calculated from mass transport across Peyer's patches and non-patch tissues derived from rabbit jejunum, and a human colon cell line (Caco-2) grown as a monolayer on polycarbonate filters. Size distribution of dextrans did not change upon transport as judged from size exclusion chromatography. Permeabilities decreased in a size-dependent manner. Ranking of permeabilities for dextran 10 and 40 kD were: Caco-2 > non-patch tissue > Peyer's patches; while dextran 70 kD demonstrated no difference among the barriers. Tissue resistance, expressed as 1/(permeability.tissue thickness) was virtually the same in Peyer's patches and non-patch tissue, suggesting that tissue thickness and not interaction determines the difference in permeability. ATP depletion with ouabain, Na(+)-azide and 2-deoxy-D-glucose, and low temperature (4 degrees C) did not result in reduced permeabilities suggesting passive transport. The results suggest that the investigated intestinal barriers transport dextrans in a similar fashion independent of their source. However, comparison of the ratios dextran 10 kD/mannitol and PEG 900/mannitol between rabbit tissue and Caco-2 monolayers suggests Caco-2 monolayers may serve as a model to study absorption potential of potentially harmful compounds in coeliac disease, gastroenteritis, and colon carcinoma.
通过对来自兔空肠的派尔集合淋巴结和非派尔集合淋巴结组织以及在聚碳酸酯滤膜上单层生长的人结肠癌细胞系（Caco-2）进行物质转运，计算了14C标记的右旋糖酐（10、40和70kD）的体外渗透率。根据尺寸排阻色谱法判断，右旋糖酐的尺寸分布在转运后没有变化。渗透率以尺寸依赖的方式降低。10kD和40kD右旋糖酐的渗透率排序为：Caco-2＞非派尔集合淋巴结组织＞派尔集合淋巴结；而70kD右旋糖酐在各屏障间无差异。以1/（渗透率·组织厚度）表示的组织阻力在派尔集合淋巴结和非派尔集合淋巴结组织中几乎相同，这表明是组织厚度而非相互作用决定了渗透率的差异。用哇巴因、叠氮化钠和2-脱氧-D-葡萄糖使ATP耗竭以及低温（4℃）并未导致渗透率降低，提示为被动转运。结果表明，所研究的肠道屏障以类似方式转运右旋糖酐，与它们的来源无关。然而，比较兔组织和Caco-2单层之间10kD右旋糖酐/甘露醇和聚乙二醇900/甘露醇的比率表明，Caco-2单层可作为研究乳糜泻、肠胃炎和结肠癌中潜在有害化合物吸收潜力的模型。
