Gotteland M, Araya M, Pizarro F, Olivares M
Laboratory of Microminerals, Institute of Nutrition and Food Technology, University of Chile, Santiago.
Dig Dis Sci. 2001 Sep;46(9):1909-14. doi: 10.1023/a:1010683014390.
In vitro studies indicate that treating cells with copper results in alteration of tight junction permeability. In humans, ingestion of a single bolus of up to 10 mg Cu/L (as copper sulfate) causes nausea and vomiting in approximately 20 and 5% of the volunteers, respectively. To understand better the gastric and intestinal effects of copper, in this study we evaluated in asymptomatic volunteers (1) the effects of acute copper ingestion on gastric and intestinal permeability and (2) whether the appearance of gastrointestinal symptoms is associated with changes in mucosal permeability. Thirty-one asymptomatic subjects were assessed in a randomized, double-blind, crossover study that included two permeability tests, one after ingesting 200 ml distilled water and the other after ingesting 200 ml water containing 10 mg Cu/L (as copper sulfate). Fifteen minutes after ingestion subjects drank a second solution containing 40 g sucrose, 7.5 g lactulose, and 2 g mannitol, and urine was collected for 5 hr. Sugar concentrations were determined by gas chromatography. Symptoms during the trials were recorded in self-administered questionnaires. Ingestion of the 10 mg/L copper solution significantly increased gastric permeability to sucrose [20.8 (11.8-73.4) vs 28.4 (16.6-113.9) mg, respectively; P = 0.0064] but did not change intestinal permeability to lactulose/mannitol [0.87 (0.53-2.06) vs 1.17 (0.58-2.39)%, respectively; P = 0.18]. Gastrointestinal symptoms were reported during both the basal and the experimental conditions, but after copper ingestion they increased to 22.6% of the subjects and were significantly more intense than under basal conditions (P = 0.047). However, changes in permeability were not related to the appearance of symptoms. These results indicate that acute oral exposure to 10 mg Cu/L exerts an effect on gastric but not intestinal mucosa, reducing the gastric mucosal barrier capacity, independently of the appearance of gastrointestinal symptoms.
体外研究表明，用铜处理细胞会导致紧密连接通透性改变。在人类中，单次摄入高达10毫克/升的铜（以硫酸铜形式），分别会使约20%和5%的志愿者出现恶心和呕吐。为了更好地了解铜对胃和肠道的影响，在本研究中，我们评估了无症状志愿者：（1）急性摄入铜对胃和肠道通透性的影响；（2）胃肠道症状的出现是否与黏膜通透性变化有关。在一项随机、双盲、交叉研究中评估了31名无症状受试者，该研究包括两项通透性测试，一项在摄入200毫升蒸馏水后进行，另一项在摄入200毫升含10毫克/升铜（以硫酸铜形式）的水后进行。摄入后15分钟，受试者饮用第二种溶液，其中含有40克蔗糖、7.5克乳果糖和2克甘露醇，并收集5小时的尿液。通过气相色谱法测定糖浓度。试验期间的症状通过自行填写的问卷记录。摄入10毫克/升的铜溶液显著增加了胃对蔗糖的通透性[分别为20.8（11.8 - 73.4）毫克和28.4（16.6 - 113.9）毫克；P = 0.0064]，但未改变肠道对乳果糖/甘露醇的通透性[分别为0.87（0.53 - 2.06）%和1.17（0.58 - 2.39）%；P = 0.18]。在基础状态和实验状态下均有胃肠道症状报告，但摄入铜后，出现症状的受试者增加到22.6%，且症状明显比基础状态下更严重（P = 0.047）。然而，通透性的变化与症状的出现无关。这些结果表明，急性口服接触10毫克/升铜对胃黏膜而非肠道黏膜有影响，降低了胃黏膜屏障能力，且与胃肠道症状的出现无关。
