Souba W W, Strebel F R, Bull J M, Copeland E M, Teagtmeyer H, Cleary K
Department of Surgery and Biochemistry, University of Florida School of Medicine, Gainesville 32610.
J Surg Res. 1988 Jun;44(6):720-6. doi: 10.1016/0022-4804(88)90106-0.
The effects of progressive malignant disease on gut/liver glutamine metabolism were studied in order to gain further insight into the altered glutamine metabolism that characterizes the host with cancer and to further elucidate the causes and consequences of glutamine depletion in tumor-bearing rats. Rats were inoculated on Day 0 with 2 X 10(6) viable fibrosarcoma cells and blood glutamine was measured every 6 days. On Day 24 the animals underwent laparotomy and sampling of arterial, portal venous, and hepatic venous blood. Arterial glutamine fell by more than one-third in tumor-bearing rats and the arterial-portal venous concentration difference for glutamine across the intestinal tract was diminished by 50% (P less than 0.01). Simultaneously the fractional extraction of glutamine by the gut was reduced from 21 to 15% (P less than 0.05). The liver switched from an organ of near glutamine balance in control rats to one of marked glutamine output in tumor-bearing rats (P less than 0.01). The wet weight of the small intestine was diminished by 15% in tumor-bearing rats and villous height was uniformly decreased in tumor-bearing rats with an average reduction in villous height of 26% (P less than 0.05). The causes of glutamine depletion in this tumor-bearing rat model remain unclear. The growing tumor may behave as a glutamine trap but also appears to alter glutamine metabolism in vital metabolic processing centers such as the gut and liver. Malignant cells may compete with gut mucosal cells for glutamine resulting in a diminished gut glutamine utilization and detrimental changes in mucosal architecture.(ABSTRACT TRUNCATED AT 250 WORDS)
为了更深入了解癌症宿主所特有的谷氨酰胺代谢改变，并进一步阐明荷瘤大鼠谷氨酰胺耗竭的原因及后果，研究了进行性恶性疾病对肠道/肝脏谷氨酰胺代谢的影响。在第0天给大鼠接种2×10⁶个活的纤维肉瘤细胞，每6天测量一次血谷氨酰胺。在第24天，对动物进行剖腹手术并采集动脉血、门静脉血和肝静脉血样本。荷瘤大鼠的动脉谷氨酰胺下降超过三分之一，肠道内谷氨酰胺的动静脉浓度差降低了50%（P<0.01）。同时，肠道对谷氨酰胺的摄取分数从21%降至15%（P<0.05）。肝脏从对照大鼠中接近谷氨酰胺平衡的器官转变为荷瘤大鼠中显著输出谷氨酰胺的器官（P<0.01）。荷瘤大鼠的小肠湿重减少了15%，荷瘤大鼠的绒毛高度均一降低，绒毛高度平均降低26%（P<0.05）。在这个荷瘤大鼠模型中谷氨酰胺耗竭的原因仍不清楚。生长中的肿瘤可能起到谷氨酰胺陷阱的作用，但似乎也会改变肠道和肝脏等重要代谢处理中心的谷氨酰胺代谢。恶性细胞可能与肠道黏膜细胞竞争谷氨酰胺，导致肠道对谷氨酰胺的利用减少以及黏膜结构发生有害变化。（摘要截短于250字）
