De Blaauw I, Deutz N E, van der Hulst R R, von Meyenfeldt M F
Department of Surgery, Faculty II, University of Limburg, Maastricht, The Netherlands.
Gastroenterology. 1997 Jan;112(1):118-26. doi: 10.1016/s0016-5085(97)70226-9.
BACKGROUND & AIMS: Glutamine is an essential amino acid for rapidly dividing cells such as enterocytes. The progress of cancer is associated with a decrease of arterial and muscle glutamine concentrations. The aim of this study was to test whether increasing tumor loads affect gut intracellular glutamine handling, protein turnover, and gut absorptive and barrier function.
Methylcholantrene-induced tumor-bearing rats were studied with a subcutaneous tumor load of 5%-15% or 15%-30% of body weight. Portal drained visceral net uptake or release of energy substrates, amino acids, and intestinal protein turnover were studied. Gut absorptive capacity and permeability was assessed by the urinary recovery of 3-O-methyl-D-glucose or lactulose-rhamnose ratio after an oral gavage.
In tumor-bearing rats, the net uptake of energy substrates (ketones and glutamine) and net protein synthesis increased across the portal drained viscera, whereas mucosal glutamine concentrations decreased. Absorptive capacity remained unchanged in both tumor-bearing groups. However, the lactulose-rhamnose ratio increased with increasing tumor load, indicating loss of gut barrier function. This was not related to changes in villus height, crypt depth, or changes in mucosal cell populations but to decreased intracellular polyamine concentrations.
The presence of a methylcholantrene tumor leads to altered mucosal glutamine metabolism and loss of gut barrier function possibly related to disturbed proliferation or differentiation of enterocytes.
谷氨酰胺是诸如肠上皮细胞等快速分裂细胞所必需的氨基酸。癌症进展与动脉血和肌肉中谷氨酰胺浓度降低相关。本研究旨在测试肿瘤负荷增加是否会影响肠道细胞内谷氨酰胺的处理、蛋白质周转以及肠道吸收和屏障功能。
对甲基胆蒽诱导的荷瘤大鼠进行研究，皮下肿瘤负荷为体重的5%-15%或15%-30%。研究门静脉引流内脏对能量底物、氨基酸的净摄取或释放以及肠道蛋白质周转。通过口服灌胃后尿中3-O-甲基-D-葡萄糖的回收率或乳果糖-鼠李糖比率评估肠道吸收能力和通透性。
在荷瘤大鼠中，门静脉引流内脏对能量底物（酮类和谷氨酰胺）的净摄取和净蛋白质合成增加，而黏膜谷氨酰胺浓度降低。两个荷瘤组的吸收能力均保持不变。然而，随着肿瘤负荷增加，乳果糖-鼠李糖比率升高，表明肠道屏障功能丧失。这与绒毛高度、隐窝深度或黏膜细胞群体的变化无关，而是与细胞内多胺浓度降低有关。
甲基胆蒽肿瘤的存在导致黏膜谷氨酰胺代谢改变和肠道屏障功能丧失，这可能与肠上皮细胞增殖或分化紊乱有关。
