SITE AND MECHANISM OF ENHANCED GASTROINTESTINAL ABSORPTION OF ALUMINUM BY CITRATE
SITE AND MECHANISM OF ENHANCED GASTROINTESTINAL ABSORPTION OF ALUMINUM BY CITRATE
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DOI：
10.1038/ki.1989.290
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发表时间：
1989-12-01
影响因子：
19.6
通讯作者：
ALFREY, AC
中科院分区：
文献类型：
--
作者：
FROMENT, DP;MOLITORIS, BA;ALFREY, AC
临床和实验研究表明，柠檬酸盐可明显促进铝的肠道吸收，但促进吸收的部位和机制尚不清楚。为了确定柠檬酸铝（Alcitr）在胃肠道中的吸收位置，在雄性Sprague-Dawley大鼠中用D-[1- 3 H]葡萄糖灌胃Alcitr。血浆Al水平迅速升高，并与D-[1-3G]葡萄糖同时达到峰值，表明早期近端肠吸收。在体外十二指肠和空肠外翻肠制备，Alcitr孵育导致组织铝水平增加，并显着增强A1和citr的跨壁转运。与citr不同，A1的跨壁运动与温度无关（37 ℃对4 ℃）。另一方面，乳酸铝（al Lac）增加组织相关。铝水平，但没有影响透壁铝运动。为了确定Alcitr给药后这种大的Al通量是否是由于细胞旁运动，使用钌红和Ussing室研究来评价细胞紧密连接的形态学和功能完整性。Alctir，而不是氯化铝，显着增加钌红沉积在细胞间隙，特别是杯状细胞周围，并诱导长期显着降低跨壁电阻。Alcitr还导致游离钙的快速和几乎完全（99.7%）螯合，这是一种已知破坏细胞紧密连接完整性的事件。综上所述，这些数据表明，由于细胞紧密连接的打开，Alcitr给药后，近端肠道中通过细胞旁途径发生铝吸收增强。
Clinical and experimental studies have shown that citrate markedly enhances the intestinal absorption of aluminum (Al), but the site and mechanism of enhanced absorption ore unknown. To determine where in the gastrointestinal tract aluminum citrate (Alcitr) was absorbed, Alcitr was gavaged with D-[1-3H] glucose in male Sprague-Dawley rats. Plasma Al levels increased rapidly and simultaneously peaked with D-[1-3G] glucose, suggesting early proximal bowel absorption. In in vitro duodenal and jejunal everted gut preparations, Alcitr incubation resulted in increased tissue Al levels and markedly enhanced transmural transport of A1 and citr. Unlike citr, the transmural movement of A1 was independent of temperature (37.degree.C vs. 4.degree.C). On the other hand, Al lactate (al Lac) increased tissue associated. Al levels but had no effect on transmural Al movement. To determine if this large flux of Al following Alcitr administration was due to paracellular movement, ruthenium red and Ussing chamber studies were used to evaluate the morpholoigic and functional integrity of cellular tight junctions. Alctir, as opposed to AlCl3, markedly increased ruthenium red deposits in intercellular spaces, especially around goblet cells, and induced a prolonged significant reduction in transmural resistance. Alcitr also resulted in rapid and nearly complete (99.7%) chelation of free calcium, an event known to disrupt cellular tight junction integrity. Taken together, these data suggest that enhanced Al absorption following administration of Alcitr occurs in the proximal bowel via the paracellular pathway due to the opening of cellular tight junctions.