van Lanschot J J, Mealy K, Wilmore D W
Laboratory for Surgical Metabolism and Nutrition, Brigham and Women's Hospital, Harvard Medical School, Boston 02115.
Ann Surg. 1990 Dec;212(6):663-70. doi: 10.1097/00000658-199012000-00003.
Tumor necrosis factor (TNF), a polypeptide produced predominantly by activated macrophages, is an important mediator of sepsis. We analyzed the specific metabolic changes that occur in the gut following TNF administration. Following general anesthesia, hemodynamic and metabolic indices were measured serially in control dogs (n = 7) and animals receiving a continuous sublethal intravenous infusion of TNF (0.57.10(5) IU/kg/6 hours, n = 7). During TNF infusion mean arterial pressure gradually decreased despite fluid administration, which maintained wedge pressure and cardiac index, which were similar to control animals. While TNF significantly reduced intestinal blood flow to 12 +/- 3 mL/min/kg compared to 28 +/- 3 mL/min/kg (p less than 0.01) in controls, intestinal oxygen consumption was maintained due to an increased extraction rate. Despite hypoperfusion the intestinal exchange of metabolic substrate (glucose, lactate, pyruvate, alanine, glutamine, glutamate, and ammonia) was comparable between the control and TNF-infused animals. However, when substrate carbon balance across the intestinal tract was calculated, it appeared that there was a limitation in fuel availability in the TNF animals. This may be due to competition for fuel between the gut and other major organs. Fuel limitation may jeopardize rapid cell proliferation and mucosal repair and with regional hypoperfusion these processes may account for the mucosal ulcerations observed at the termination of the study.
肿瘤坏死因子（TNF）是一种主要由活化巨噬细胞产生的多肽，是脓毒症的重要介质。我们分析了给予TNF后肠道中发生的特定代谢变化。全身麻醉后，连续测量对照犬（n = 7）和接受连续亚致死剂量静脉输注TNF（0.5×10⁵IU/kg/6小时，n = 7）动物的血流动力学和代谢指标。在TNF输注期间，尽管补液，平均动脉压仍逐渐下降，而楔压和心脏指数得以维持，与对照动物相似。与对照组的28±3 mL/min/kg相比，TNF显著降低肠道血流量至12±3 mL/min/kg（p<0.01），但由于提取率增加，肠道氧耗得以维持。尽管存在灌注不足，但对照动物和输注TNF动物之间代谢底物（葡萄糖、乳酸、丙酮酸、丙氨酸、谷氨酰胺、谷氨酸和氨）的肠道交换相当。然而，当计算肠道内底物碳平衡时，似乎TNF处理的动物存在燃料供应限制。这可能是由于肠道与其他主要器官之间对燃料的竞争。燃料限制可能危及细胞的快速增殖和黏膜修复，并且在局部灌注不足的情况下，这些过程可能是研究结束时观察到黏膜溃疡的原因。
