连续肠内给药可以克服甲氨蝶呤诱导的胃肠道粘膜炎大鼠对葡萄糖的有限吸收能力。
Continuous enteral administration can overcome the limited capacity to absorb glucose in rats with methotrexate-induced gastrointestinal mucositis.
机构信息
Department of Pediatric Gastroenterology and Hepatology, Beatrix Children's Hospital, Groningen University Institute for Drug Exploration, Center for Liver, Digestive and Metabolic Diseases, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
出版信息
Support Care Cancer. 2013 Mar;21(3):863-71. doi: 10.1007/s00520-012-1597-2. Epub 2012 Sep 26.
BACKGROUND
Patients with chemotherapy-induced gastrointestinal mucositis often suffer from weight loss. It is not well known how to enterally feed mucositis patients, potentially experiencing malabsorption. Recently, we showed in a rat model of methotrexate (MTX)-induced mucositis that intestinal absorption of glucose in trace amounts is still intact. We now determined the quantitative capacity to absorb glucose in rats with mucositis, relative to controls.
METHODS
We administered a physiologically relevant amount of [1-(13)C]glucose-enriched glucose (meal size) as a bolus by oral gavage (2 g/kg once) or continuously by intraduodenal infusion (±1.9 g/(kg·h) for 5 h) to rats with MTX-induced mucositis and controls. Blood [1-(13)C]glucose concentrations were determined during the experimental period. To calculate the quantitative absorptive capacity, Steele's one-compartment model, including simultaneous intravenous infusion of [6,6-(2)H(2)]glucose, was used. After the experiment, jejunal histology and plasma citrulline concentrations were assessed.
RESULTS
MTX-induced mucositis was confirmed by a reduction in villus length and plasma citrulline (both -57%, relative to controls, P < 0.01). When glucose was administered as a bolus, MTX-treated rats only absorbed 15% of administered glucose, compared with 85% in controls (medians, P < 0.01). Upon continuous intraduodenal glucose infusion, the median absorptive capacity for glucose in MTX-treated rats did not differ from controls (80 versus 93% of administered glucose respectively, P = 0.06). However, glucose absorption differed substantially between individual MTX-treated rats (range, 21-95%), which correlated poorly with villus length (rho = 0.54, P = 0.030) and plasma citrulline (rho = 0.56, P = 0.024).
CONCLUSION
Continuous enteral administration can almost completely overcome the reduced absorptive capacity for glucose in rats with mucositis.
背景
接受化疗引起的胃肠道粘膜炎的患者常出现体重减轻。目前尚不清楚如何对可能经历吸收不良的粘膜炎患者进行肠内喂养。最近，我们在甲氨蝶呤（MTX）诱导的粘膜炎大鼠模型中表明，痕量的肠道葡萄糖吸收仍然完整。现在，我们确定了与对照组相比，粘膜炎大鼠葡萄糖吸收的定量能力。
方法
我们通过口服管饲法（一次 2g/kg）或通过十二指肠内输注（5 小时内±1.9g/（kg·h））给予大鼠生理相关量的[1-（13）C]葡萄糖丰富的葡萄糖（餐量）。在实验期间测定血液[1-（13）C]葡萄糖浓度。为了计算定量吸收能力，使用了包括同时静脉内输注[6,6-（2）H（2）]葡萄糖的 Steele 单室模型。实验结束后，评估空肠组织学和血浆瓜氨酸浓度。
结果
通过绒毛长度和血浆瓜氨酸（均相对于对照组降低 57%，P<0.01）证实 MTX 诱导的粘膜炎。当葡萄糖作为团块给药时，MTX 处理的大鼠仅吸收了给予葡萄糖的 15%，而对照组则吸收了 85%（中位数，P<0.01）。在连续的十二指肠内葡萄糖输注时，MTX 处理的大鼠的葡萄糖吸收能力中位数与对照组无差异（分别为给予葡萄糖的 80%和 93%，P=0.06）。然而，MTX 处理的大鼠之间的葡萄糖吸收差异很大（范围为 21%-95%），与绒毛长度相关性差（rho=0.54，P=0.030）和血浆瓜氨酸（rho=0.56，P=0.024）。
结论
连续肠内给药几乎可以完全克服粘膜炎大鼠葡萄糖吸收能力降低的问题。
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