Troost Freddy J, Brummer Robert-Jan M, Haenen Guido R M M, Bast Aalt, van Haaften Rachel I, Evelo Chris T, Saris Wim H M
Department of Internal Medicine/Gastroenterology, Maastricht University, Maastricht, The Netherlands.
Physiol Genomics. 2006 Apr 13;25(2):242-9. doi: 10.1152/physiolgenomics.00114.2005. Epub 2006 Feb 7.
Iron-induced oxidative stress in the small intestine may alter gene expression in the intestinal mucosa. The present study aimed to determine which genes are mediated by an iron-induced oxidative challenge in the human small intestine. Eight healthy volunteers [22 yr(SD2)] were tested on two separate occasions in a randomized crossover design. After duodenal tissue sampling by gastroduodenoscopy, a perfusion catheter was inserted orogastrically to perfuse a 40-cm segment of the proximal small intestine with saline and, subsequently, with either 80 or 400 mg of iron as ferrous gluconate. After the intestinal perfusion, a second duodenal tissue sample was obtained. Thiobarbituric acid-reactive substances, an indicator of lipid peroxidation, in intestinal fluid samples increased significantly and dose dependently at 30 min after the start of perfusion with 80 or 400 mg of iron, respectively (P < 0.001). During the perfusion with 400 mg of iron, the increase in thiobarbituric acid-reactive substances was accompanied by a significant, momentary rise in trolox equivalent antioxidant capacity, an indicator of total antioxidant capacity (P < 0.05). The expression of 89 gene reporters was significantly altered by both iron interventions. Functional mapping showed that both iron dosages mediated six distinct processes. Three of those processes involved G-protein receptor coupled pathways. The other processes were associated with cell cycle, complement activation, and calcium channels. Iron administration in the small intestine induced dose-dependent lipid peroxidation and a momentary antioxidant response in the lumen, mediated the expression of at least 89 individual gene reporters, and affected at least six biological processes.
铁诱导的小肠氧化应激可能会改变肠黏膜中的基因表达。本研究旨在确定在人类小肠中哪些基因是由铁诱导的氧化应激所介导的。八名健康志愿者[22岁（标准差2）]在随机交叉设计下分两次进行测试。通过胃十二指肠镜进行十二指肠组织采样后，经口插入灌注导管，先用生理盐水灌注近端小肠的40厘米段，随后分别用80毫克或400毫克葡萄糖酸亚铁进行灌注。小肠灌注后，获取第二份十二指肠组织样本。在分别用80毫克或400毫克铁开始灌注后30分钟，肠液样本中的硫代巴比妥酸反应性物质（脂质过氧化的指标）显著且呈剂量依赖性增加（P<0.001）。在用400毫克铁灌注期间，硫代巴比妥酸反应性物质的增加伴随着总抗氧化能力指标——Trolox等效抗氧化能力的显著瞬间升高（P<0.05）。两种铁干预均显著改变了89种基因报告分子的表达。功能图谱显示，两种铁剂量均介导了六个不同的过程。其中三个过程涉及G蛋白偶联途径。其他过程与细胞周期、补体激活和钙通道有关。小肠中铁的给药诱导了剂量依赖性的脂质过氧化和肠腔内的瞬间抗氧化反应，介导了至少89种单个基因报告分子的表达，并影响了至少六个生物学过程。
