de Blaauw Ivo, Schols Annemie M W J, Koerts-deLang Esther, Wouters Emiel F M, Deutz Nicolaas E P
Department of Surgery, Maastricht University, The Netherlands.
Clin Nutr. 2004 Oct;23(5):1035-42. doi: 10.1016/j.clnu.2004.01.004.
Corticosteroid treatment affects muscle protein and glutamine metabolism. In the present study we aimed to clarify to what extent anorexia, weight loss and corticosteroids determine protein and glutamine metabolism in muscle.
The study was performed in Wistar rats (300-350 g, n = 40) given triamcinolone (0.25 mg/kg/day i.m.) treatment (CS group) for 14 days, sham treated free fed (FF group), sham treated pair fed (PF group) and sham treated pair weight (PW group). In vivo protein and glutamine turnover were measured using L-[2,6-3H]phenylalanine and L-[3,4-3H]glurtamine as tracer in a three compartment model across the hindquarter.
Corticosteroid treatment decreased total body weight to a greater extent than can be explained by decreased food intake only, justifying the need for pair weight controls. Muscle weight loss was relatively greater in the corticosteroid treated rats than in the pair weight controls indicating specific corticosteroid induced changes in muscle protein metabolism. Pair weight rats increased muscle net protein breakdown rates from -5 +/- 3 nmol x 100 g body weight(-1) x min(-1) to -15 +/- 3 nmol x 100 g body weight(-1) x min(-1) (P < 0.05 vs FF). In the corticosteroid treated rats net protein breakdown rates increased to -22 +/- 4 nmol x 100 g body weight(-1) x min(-1) (P < 0.01 CS vs FF/PF) Net protein breakdown in corticosteroid treated rats was accompanied by increased glutamine efflux from the hindquarter (P < 0.05, CS vs FF/PF/PW). The latter could predominantly be explained by de novo synthesis. Furthermore, corticosteroid treatment induced a loss of plasma to free muscle glutamine gradient indicating down regulation of glutamine membrane transport rates into muscle. This effect was, however, similar in the pair weight control group and can thus be fully accounted for by the muscle weight loss.
Two weeks treatment with triamcinolone increases net in vivo protein breakdown of muscle directly and indirectly due to secondary weight loss and decreased food intake. The amino acid residues are used for glutamine de novo synthesis which is exported from muscle to visceral organs by down regulation of glutamine transport systems. These changes were in majority related to muscle weight loss.
皮质类固醇治疗会影响肌肉蛋白质和谷氨酰胺代谢。在本研究中，我们旨在阐明厌食、体重减轻和皮质类固醇在多大程度上决定肌肉中的蛋白质和谷氨酰胺代谢。
本研究在体重300 - 350克的Wistar大鼠（n = 40）中进行，给予曲安西龙（0.25毫克/千克/天，肌肉注射）治疗14天（CS组），假手术自由进食组（FF组）、假手术配对进食组（PF组）和假手术配对体重组（PW组）。使用L - [2,6 - 3H]苯丙氨酸和L - [3,4 - 3H]谷氨酰胺作为示踪剂，在一个三室模型中跨后肢测量体内蛋白质和谷氨酰胺周转率。
皮质类固醇治疗导致总体重下降的程度大于仅由食物摄入量减少所解释的程度，这证明了需要进行配对体重对照。与配对体重对照组相比，皮质类固醇治疗的大鼠肌肉重量损失相对更大，表明皮质类固醇特异性地诱导了肌肉蛋白质代谢的变化。配对体重的大鼠肌肉净蛋白质分解率从-5±3纳摩尔×100克体重-1×分钟-1增加到-15±3纳摩尔×100克体重-1×分钟-1（与FF组相比，P < 0.05）。在皮质类固醇治疗的大鼠中，净蛋白质分解率增加到-22±4纳摩尔×100克体重-1×分钟-1（与FF/PF组相比，CS组P < 0.01）。皮质类固醇治疗的大鼠净蛋白质分解伴随着后肢谷氨酰胺外流增加（与FF/PF/PW组相比，CS组P < 0.05）。后者主要可由从头合成来解释。此外，皮质类固醇治疗导致血浆与游离肌肉谷氨酰胺梯度降低，表明谷氨酰胺向肌肉的膜转运速率下调。然而，这种效应在配对体重对照组中也相似，因此可以完全由肌肉重量减轻来解释。
曲安西龙两周治疗直接和间接增加了肌肉的体内净蛋白质分解，这是由于继发性体重减轻和食物摄入量减少所致。氨基酸残基用于谷氨酰胺的从头合成，通过下调谷氨酰胺转运系统从肌肉输出到内脏器官。这些变化大多与肌肉重量减轻有关。
