Cragg R A, Phillips S R, Piper J M, Varma J S, Campbell F C, Mathers J C, Ford D
Institute for Cell and Molecular Biosciences, University of Newcastle, The Medical School, Newcastle upon Tyne NE2 4HH, UK.
Gut. 2005 Apr;54(4):469-78. doi: 10.1136/gut.2004.041962.
The role of intestinal transporter regulation in optimising nutrient absorption has been studied extensively in rodent and cell line models but not in human subjects.
The aim of the present study was to investigate the response in vivo of zinc transporters in the human enterocyte to dietary zinc supplementation.
Eighteen patients who had previously undergone ileostomy, all free of any symptoms of inflammatory bowel disease.
Subjects took a daily zinc supplement of 25 mg for 14 days in a double blind, placebo controlled, crossover trial. The effect of the supplement on expression in ileal biopsies of the zinc transporters SLC30A1, SLC30A4, SLC30A5, SLC39A1, SLC39A4, and metallothionein was measured by reverse transcription-polymerase chain reaction RT-PCR. Expression of SLC30A1, SLC30A5, and SLC39A4 was also examined by immunoblotting.
The zinc supplement reduced SLC30A1 mRNA (1.4-fold) together with SLC30A1, SLC30A5, and SLC39A4 protein (1.8-fold, 3.7-fold, and to undetectable levels, respectively) in ileal mucosa and increased metallothionein mRNA (1.7-fold). The supplement had no effect on expression of SLC30A4 or SLC39A1 mRNA. Localisation of SLC30A5 at the apical human enterocyte/colonocyte membrane and also at the apical membrane of Caco-2 cells was demonstrated by immunohistochemistry. Commensurate with these observations in zinc supplemented human subjects, SLC30A1, SLC30A5, and SLC39A4 mRNA and protein were reduced in Caco-2 cells cultured at 200 muM compared with 100 muM zinc.
These observations indicate that, in response to variations in dietary zinc intakes, regulated expression of plasma membrane zinc transporters in the human intestine contributes to maintenance of zinc status.
肠道转运体调节在优化营养物质吸收中的作用已在啮齿动物和细胞系模型中得到广泛研究，但尚未在人类受试者中进行研究。
本研究旨在调查人类肠细胞中锌转运体对膳食锌补充的体内反应。
18名曾接受回肠造口术的患者，均无任何炎症性肠病症状。
在一项双盲、安慰剂对照、交叉试验中，受试者每天服用25毫克锌补充剂，持续14天。通过逆转录-聚合酶链反应（RT-PCR）测量补充剂对锌转运体SLC30A1、SLC30A4、SLC30A5、SLC39A1、SLC39A4和金属硫蛋白在回肠活检组织中表达的影响。还通过免疫印迹法检测了SLC30A1、SLC30A5和SLC39A4的表达。
锌补充剂使回肠黏膜中SLC30A1 mRNA（1.4倍）以及SLC30A1、SLC30A5和SLC39A4蛋白（分别为1.8倍、3.7倍和降至检测不到的水平）降低，并使金属硫蛋白mRNA增加（1.7倍）。补充剂对SLC30A4或SLC39A1 mRNA的表达没有影响。免疫组织化学显示SLC30A5定位于人类肠细胞/结肠细胞顶端膜以及Caco-2细胞的顶端膜。与这些在补充锌的人类受试者中的观察结果一致，与100μM锌培养的Caco-2细胞相比，在200μM锌培养的Caco-2细胞中，SLC30A1、SLC30A5和SLC39A4 mRNA和蛋白减少。
这些观察结果表明，响应膳食锌摄入量的变化，人类肠道中质膜锌转运体的调节表达有助于维持锌状态。
