Bours Martijn J, Troost Freddy J, Brummer Robert-Jan M, Bast Aalt, Dagnelie Pieter C
Department of Epidemiology, Maastricht University, Nutrition and Toxicology Research Institute Maastricht, Maastricht, The Netherlands.
Eur J Gastroenterol Hepatol. 2007 Mar;19(3):245-50. doi: 10.1097/MEG.0b013e328011093c.
Nonsteroidal anti-inflammatory drug (NSAID) use is associated with an elevated risk of gastrointestinal damage. As adenosine 5'-triphosphate (ATP) may play a protective role in the small intestine, our objective was to determine the local effect of ATP on small intestinal permeability changes induced by short-term challenge of the NSAID indomethacin in healthy humans.
Mucosal permeability of the small intestine was assessed by the lactulose/rhamnose permeability test, that is, ingestion of a test drink containing 5 g lactulose and 0.5 g L-rhamnose followed by total urine collection for 5 h. Urinary excretion of lactulose and L-rhamnose was determined by fluorescent detection high-pressure liquid chromatography (HPLC). Basal small intestinal permeability was assessed as a control condition. As a model of increased small intestinal permeability, two doses of indomethacin were ingested before ingestion of the test drink (75 mg and 50 mg at 10 h and 1 h before the test drink, respectively). Concomitantly with indomethacin ingestion, placebo or 30 mg/kg ATP was administered through a naso-intestinal tube.
Median urinary lactulose/rhamnose ratio (g/g) in the control condition was 0.023 (interquartile range: 0.013-0.041). Compared with the control condition, urinary lactulose/rhamnose ratio after ingestion of indomethacin and administration of placebo was significantly increased [0.042 (0.028-0.076); P<0.01]. In contrast, urinary lactulose/rhamnose ratio after indomethacin ingestion plus ATP administration [0.027 (0.020-0.046)] was significantly lower than the lactulose/rhamnose ratio in the placebo condition (P<0.01).
Topical ATP administration into the small intestine during short-term challenge of the NSAID indomethacin attenuates the NSAID-induced increase in small intestinal permeability in healthy humans.
非甾体抗炎药（NSAID）的使用与胃肠道损伤风险升高相关。由于腺苷5'-三磷酸（ATP）可能在小肠中发挥保护作用，我们的目的是确定ATP对健康人短期服用NSAID吲哚美辛引起的小肠通透性变化的局部影响。
通过乳果糖/鼠李糖通透性试验评估小肠黏膜通透性，即摄入含有5g乳果糖和0.5g L-鼠李糖的试验饮料，随后收集5小时的全部尿液。通过荧光检测高压液相色谱法（HPLC）测定乳果糖和L-鼠李糖的尿排泄量。作为对照条件，评估基础小肠通透性。作为小肠通透性增加的模型，在摄入试验饮料前分别于10小时和1小时服用两剂吲哚美辛（分别为75mg和50mg）。在服用吲哚美辛的同时，通过鼻肠管给予安慰剂或30mg/kg ATP。
对照条件下尿乳果糖/鼠李糖比值（g/g）的中位数为0.023（四分位间距：0.013 - 0.041）。与对照条件相比，服用吲哚美辛并给予安慰剂后尿乳果糖/鼠李糖比值显著升高[0.042（0.028 - 0.076）；P<0.01]。相比之下，服用吲哚美辛加ATP后尿乳果糖/鼠李糖比值[0.027（0.020 - 0.046）]显著低于安慰剂条件下的乳果糖/鼠李糖比值（P<0.01）。
在短期服用NSAID吲哚美辛期间向小肠局部给予ATP可减轻NSAID诱导的健康人小肠通透性增加。
