Douglas R G, Gluckman P D, Breier B H, McCall J L, Parry B, Shaw J H
Department of Surgery, University of Auckland, New Zealand.
Am J Physiol. 1991 Nov;261(5 Pt 1):E606-12. doi: 10.1152/ajpendo.1991.261.5.E606.
Achieving nitrogen accretion in patients with critical surgical illness or cancer cachexia is often not possible by the simple provision of calories and nitrogen. Cachexia may result from the metabolic derangements caused by release of inflammatory mediators such as tumor necrosis factor (TNF). We wished to determine whether recombinant human insulin-like growth factor I (rhIGF-I) preserves its protein-sparing effects in the face of high plasma TNF concentrations. Primed constant infusions of [15N]urea and [6-3H]glucose tracers were used to measure protein and glucose kinetics in fasted lambs. The lambs were divided into four groups: two groups received normal saline infusions of 480 min, and two groups received recombinant TNF (rTNF) infusions of 1 microgram.kg-1.h-1. During the last 300 min, one of the normal saline and one of the rTNF-infused groups were infused with rhIGF-I at a dose of 50 micrograms.kg-1.h-1. rTNF infusion resulted in the lambs becoming febrile and significantly increased plasma cortisol, glucagon, and insulin levels. rhIGF-I infusion in the control animals reduced the rate of loss of protein by 15% (P less than 0.01) and increased the rate of peripheral glucose clearance by 55% (P less than 0.01). rhIGF-I infusion in the rTNF-treated animals reduced the rate of net protein loss by 15% (P less than 0.01) and caused similar changes in glucose kinetics, as were observed in the control animals. We conclude that as rhIGF-I preserves its protein anabolic action in the face of high rTNF levels, further investigation into a possible clinical role for rhIGF-I in severe surgical illness is warranted.
对于患有严重外科疾病或癌症恶病质的患者，仅通过提供热量和氮通常无法实现氮的增加。恶病质可能是由肿瘤坏死因子（TNF）等炎症介质释放引起的代谢紊乱所致。我们希望确定重组人胰岛素样生长因子I（rhIGF-I）在高血浆TNF浓度情况下是否仍能保持其蛋白质节省作用。通过对禁食羔羊进行[15N]尿素和[6-3H]葡萄糖示踪剂的首剂持续输注来测量蛋白质和葡萄糖动力学。羔羊被分为四组：两组接受480分钟的生理盐水输注，两组接受1微克·千克-1·小时-1的重组TNF（rTNF）输注。在最后300分钟内，一组接受生理盐水输注的和一组接受rTNF输注的羔羊以50微克·千克-1·小时-1的剂量输注rhIGF-I。rTNF输注导致羔羊发热，并显著提高血浆皮质醇、胰高血糖素和胰岛素水平。对照组动物输注rhIGF-I使蛋白质丢失率降低了15%（P<0.01），外周葡萄糖清除率提高了55%（P<小于0.01）。在接受rTNF治疗的动物中输注rhIGF-I使净蛋白质丢失率降低了15%（P<0.01），并在葡萄糖动力学方面引起了与对照组动物相似的变化。我们得出结论，由于rhIGF-I在高rTNF水平情况下仍能保持其蛋白质合成作用，因此有必要进一步研究rhIGF-I在严重外科疾病中可能的临床作用。
