Intestinal barrier function and secretion in methotrexate-induced rat intestinal mucositis
Intestinal barrier function and secretion in methotrexate-induced rat intestinal mucositis
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DOI：
10.1023/b:ddas.0000011604.45531.2c
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发表时间：
2004-01-01
影响因子：
3.1
通讯作者：
Lima, AAM
中科院分区：
文献类型：
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作者：
Carneiro, BA;Lima, IPF;Lima, AAM
化疗引起的粘膜炎是一种重要的剂量限制和昂贵的副作用，目前还没有明确的预防或治疗方法。这在一定程度上是由于对其病理生理和对肠道功能的影响缺乏了解。本研究的目的是研究甲氨蝶呤诱导的粘膜炎模型的小肠屏障功能以及电解质和水的转运，并将这些变化与组织学损害相关联。给Wistar大鼠灌胃甲氨蝶呤(1.5~3.5 mg/kg)，连续3d复制粘膜炎模型。灌胃给药后，通过测定尿中乳果糖和甘露醇的排泄率来测定肠道通透性。在活体内进行肠道灌流以评估水和电解质的转运。接受甲氨蝶呤治疗的大鼠体重显著减轻，食物摄入量显著减少。甲氨蝶呤可引起十二指肠、空肠和回肠隐窝显著的和剂量依赖性的绒毛萎缩和延长。甲氨蝶呤还引起钠和钾的分泌增加，粘膜吸收表面积显著减少，表现为甘露醇排泄率的下降。总而言之，甲氨蝶呤通过破坏肠道通透性和诱导电解质分泌，同时造成组织学损害，导致小肠功能的重大变化。
Chemotherapy-induced mucositis is an important dose-limiting and costly side effect for which there is no definitive prophylaxis or treatment. This is due in part to the lack of understanding of its pathophysiology and impact on intestinal function. The objectives of this study were to investigate the small intestine barrier function and electrolyte and water transport in an experimental model of methotrexate-induced mucositis, and to correlate these alterations with histological damage. Wistar rats were treated with methotrexate (1.5-3.5 mg/kg) for 3 days to induce mucositis. Intestinal perme-ability was measured by the urinary excretion rate of lactulose and mannitol following administration by gavage. Intestinal perfusion was performed in vivo for evaluation of water and electrolyte transports. Methotrexate-treated rats lost a significant amount of weight and presented a marked reduction in food intake. Methotrexate induced significant and dose-dependent villous atrophy and elongation of crypts in duodenum, jejunum, and ileum. Methotrexate also induced an increase in sodium and potassium secretion and an important reduction of the mucosa absorptive surface area, shown by the decrease in the mannitol excretion ratio. In conclusion, methotrexate caused major changes in small bowel function by disrupting intestinal permeability and inducing electrolyte secretion in parallel with substantial histological damage.