Raina N, Jeejeebhoy K N
Department of Medicine, University of Toronto, Ontario, Canada.
Am J Clin Nutr. 1998 Dec;68(6):1284-90. doi: 10.1093/ajcn/68.6.1284.
Previous studies have shown that anorexia and reduced food intake are the main causes of weight loss in rats infused with tumor necrosis factor alpha (TNF-alpha), with no influence on corticosterone concentrations. In contrast, in clinical sepsis, muscle wasting due to increased catabolism is associated with increased corticosteroid concentrations. We hypothesized that in the rat model, corticosterone potentiates the catabolic effect of TNF-alpha in amounts that by itself does not influence muscle catabolism. Orally fed rats were divided into 3 treatment groups: continuous infusion of TNF-alpha (TNF; 100 microg x kg(-1) x d(-1)), corticosterone (Cort; 50 microg x g(-1) x d(-1)), or both (TNF+Cort). Each group was compared with a respective pair-fed (PF) group. In addition an ad libitum (AL)-fed group receiving an infusion of physiologic saline was studied to observe unrestricted food intake and weight gain. After 4 d of infusion, dietary intake and weight gain were significantly higher in the Cort and AL groups than in the TNF and TNF+Cort groups. Although wet liver weights and protein contents were significantly higher in the Cort, TNF, and TNF+Cort groups than in their respective PF group, the TNF and TNF+Cort groups had lower relative carcass weights. The weight and protein content of the diaphragm were lower and nitrogen excretion was higher in the TNF+Cort group than in the respective PF group. The results suggest that TNF-alpha plus corticosterone had a specific catabolic effect on the diaphragm. In addition, together they increased overall nitrogen excretion.
先前的研究表明,厌食和食物摄入量减少是输注肿瘤坏死因子α(TNF-α)的大鼠体重减轻的主要原因,对皮质酮浓度没有影响。相比之下,在临床脓毒症中,分解代谢增加导致的肌肉消瘦与皮质类固醇浓度升高有关。我们假设,在大鼠模型中,皮质酮会增强TNF-α的分解代谢作用,而其本身的量并不影响肌肉分解代谢。经口喂养的大鼠被分为3个治疗组:持续输注TNF-α(TNF;100μg·kg⁻¹·d⁻¹)、皮质酮(Cort;50μg·g⁻¹·d⁻¹)或两者(TNF+Cort)。每组与各自的配对喂养(PF)组进行比较。此外,还研究了一个自由进食(AL)组,该组接受生理盐水输注,以观察不受限制的食物摄入量和体重增加情况。输注4天后,Cort组和AL组的饮食摄入量和体重增加显著高于TNF组和TNF+Cort组。尽管Cort组、TNF组和TNF+Cort组的湿肝重量和蛋白质含量显著高于各自的PF组,但TNF组和TNF+Cort组的相对胴体重量较低。TNF+Cort组的膈肌重量和蛋白质含量低于各自的PF组,而氮排泄量较高。结果表明,TNF-α加皮质酮对膈肌有特定的分解代谢作用。此外,它们共同增加了总体氮排泄。