Schricker Thomas, Meterissian Sarkis, Lattermann Ralph, Adegoke Olasunkamni A J, Marliss Errol B, Mazza Louise, Eberhart Leopold, Carli Franco, Nitschman Evan, Wykes Linda
Department of Anesthesia, McGill University, Royal Victoria Hospital, Montreal, Quebec, Canada.
Ann Surg. 2008 Dec;248(6):1051-9. doi: 10.1097/SLA.0b013e31818842d8.
We tested the hypothesis that the avoidance of preoperative fasting by hypocaloric nutrition attenuates protein catabolism after surgery.
Prolonged fasting before major abdominal procedures has been demonstrated to accentuate the catabolic response to surgery.
Twenty-two patients undergoing colorectal cancer surgery were randomly assigned to receive glucose and amino acids intravenously starting either 20 hours before the operation or with surgical skin incision. Nutrition was administered until the second postoperative day, with glucose providing 50% and amino acids 20% of each patient's measured resting energy expenditure. Whole body leucine and glucose kinetics were assessed by L-[1-(13)C]leucine and [6,6-(2)H(2)]glucose before and after surgery. Fractional synthesis rates of muscle protein, albumin, and fibrinogen were determined using primed continuous infusions of L-[(2)H(5)]phenylalanine postoperatively, whereas the expression of mRNA of proteolytic genes in muscle (Mafbx/atrogin-1, ubiquitin, Murf 1) was determined by quantitative RT-PCR. Circulating concentrations of glucose, lactate, amino acids, insulin, glucagon, and cortisol were also measured. This study has been registered at ClinicalTrials.gov (Identifier: NCT00614133).
Preoperative feeding inhibited endogenous protein breakdown (fasting group: 128 +/- 23 micromol . kg(-1) . h(-1); nutrition group: 96 +/- 22 micromol . kg(-1) . h(-1); P = 0.02) and blunted the increase in amino acid oxidation (fasting group: 27 +/- 5 micromol . kg(-1) . h(-1); nutrition group: 20 +/- 5 micromol . kg(-1) . h(-1); P = 0.03), resulting in positive whole-body protein balance after surgery (fasting group: -10 +/- 4 micromol . kg(-1) . h(-1); nutrition group: 1 +/- 3 micromol . kg(-1) . h(-1); P < 0.001). This anabolic response was associated with decreased muscle proteolytic gene expression and increased hepatic albumin synthesis. Total plasma protein, fibrinogen, and muscle protein synthesis were not affected.
Hypocaloric nutrition decreases protein catabolism, with a contribution from the ubiquitin pathway in muscle, and stimulates albumin synthesis after colorectal surgery if initiated 1 day before the operation.
我们检验了如下假设，即通过低热量营养避免术前禁食可减轻术后蛋白质分解代谢。
大型腹部手术前长时间禁食已被证明会加剧对手术的分解代谢反应。
22例行结直肠癌手术的患者被随机分配，分别于手术前20小时或手术皮肤切开时开始静脉输注葡萄糖和氨基酸。营养支持持续至术后第二天，葡萄糖提供每位患者测量静息能量消耗的50%，氨基酸提供20%。术前和术后通过L-[1-(13)C]亮氨酸和[6,6-(2)H(2)]葡萄糖评估全身亮氨酸和葡萄糖动力学。术后使用L-[(2)H(5)]苯丙氨酸连续输注负荷剂量法测定肌肉蛋白、白蛋白和纤维蛋白原的分数合成率，而通过定量逆转录聚合酶链反应测定肌肉中蛋白水解基因（Mafbx/atrogin-1、泛素、Murf 1）的mRNA表达。还测量了循环中的葡萄糖、乳酸、氨基酸、胰岛素、胰高血糖素和皮质醇浓度。本研究已在ClinicalTrials.gov注册（标识符：NCT00614133）。
术前喂养抑制了内源性蛋白质分解（禁食组：128±23微摩尔·千克(-1)·小时(-1)；营养组：96±22微摩尔·千克(-1)·小时(-1)；P = 0.02），并减弱了氨基酸氧化的增加（禁食组：27±5微摩尔·千克(-1)·小时(-1)；营养组：20±5微摩尔·千克(-1)·小时(-1)；P = 0.03），导致术后全身蛋白质呈正平衡（禁食组：-10±4微摩尔·千克(-1)·小时(-1)；营养组：1±3微摩尔·千克(-1)·小时(-1)；P < 0.001）。这种合成代谢反应与肌肉蛋白水解基因表达降低和肝脏白蛋白合成增加有关。总血浆蛋白、纤维蛋白原和肌肉蛋白合成未受影响。
低热量营养可降低蛋白质分解代谢，其中肌肉中的泛素途径起到一定作用，并且如果在手术前1天开始，可刺激结直肠癌手术后的白蛋白合成。
