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大鼠体内大颗粒的跨上皮转运:一种用于颗粒摄取定量研究的新模型。

Transepithelial transport of large particles in rat: a new model for the quantitative study of particle uptake.

作者信息

Limpanussorn J, Simon L, Dayan A D

机构信息

DH Department of Toxicology, St Bartholomew's and the Royal London School of Medicine and Dentistry, UK.

出版信息

J Pharm Pharmacol. 1998 Jul;50(7):753-60. doi: 10.1111/j.2042-7158.1998.tb07136.x.

DOI:10.1111/j.2042-7158.1998.tb07136.x
PMID:9720624
Abstract

The transport of large particles across the intestinal mucosa and the mechanisms of transfer of the particles into the body are still little understood. Fluorescent polystyrene latex particles (2 microm diam.) were administered orally to young male Sprague-Dawley rats in doses of 2.33 x 10(3), 2.33 x 10(6) and 2.33 x 10(9) particles. After 60 min, Peyer's patches and Peyer's patch-free tissues were collected from the small intestine and colon. A novel technique was used to exclude non-translocated particles adherent to the mucosal surface; the intestinal epithelium was stripped from the intestine by immersion in Hanks' balanced salt solution containing 1.5 mM EDTA. Particles in solubilized samples of intact and epithelium-stripped Peyer's patches and Peyer's patch-free intestinal tissue and colon were quantified by fluorescence microscopy. The location of particles within the intact and epithelium-stripped gut samples was revealed by confocal microscopy. Particles were shown to have been taken up along the entire length of the small and large intestines via both Peyer's patches and the normal intestinal epithelium. The number of particles detected in the distal region was greater than in the proximal part of the small intestine, although the difference was not statistically significant. This study has revealed that large numbers of non-translocated particles adhered to the mucosal surface resulting in a high background count. The assay system was considerably improved by the epithelium-stripping technique. The process of transepithelial uptake is a potentially important route of uptake of toxic, immunologically active and radioactive substances. These particles are much larger than the conventionally accepted upper limit for absorbed materials.

摘要

大颗粒跨肠黏膜的转运以及颗粒进入体内的转运机制仍鲜为人知。将荧光聚苯乙烯乳胶颗粒(直径2微米)以2.33×10³、2.33×10⁶和2.33×10⁹个颗粒的剂量口服给予年轻雄性Sprague-Dawley大鼠。60分钟后,从小肠和结肠收集派尔集合淋巴结及无派尔集合淋巴结的组织。采用一种新技术排除附着于黏膜表面的未转运颗粒;通过将肠浸泡在含有1.5 mM EDTA的汉克斯平衡盐溶液中,使肠上皮从肠上剥离。通过荧光显微镜对完整的、上皮剥离后的派尔集合淋巴结以及无派尔集合淋巴结的肠组织和结肠的溶解样品中的颗粒进行定量。通过共聚焦显微镜揭示完整的和上皮剥离后的肠道样品中颗粒的位置。结果表明,颗粒通过派尔集合淋巴结和正常肠上皮在小肠和大肠的整个长度上被摄取。尽管差异无统计学意义,但在小肠远端区域检测到的颗粒数量多于近端部分。该研究表明,大量未转运的颗粒附着于黏膜表面,导致背景计数较高。上皮剥离技术显著改进了检测系统。跨上皮摄取过程是有毒、免疫活性和放射性物质摄取的一个潜在重要途径。这些颗粒比传统公认的吸收物质的上限要大得多。

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