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Preoperative overnight parenteral nutrition (TPN) improves skeletal muscle protein metabolism indicated by microarray algorithm analyses in a randomized trial

机译:术前隔夜肠外营养(TPN)改善了一项随机试验中微阵列算法分析表明的骨骼肌蛋白代谢

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摘要

Loss of muscle mass is associated with increased risk of morbidity and mortality in hospitalized patients. Uncertainties of treatment efficiency by short‐term artificial nutrition remain, specifically improvement of protein balance in skeletal muscles. In this study, algorithmic microarray analysis was applied to map cellular changes related to muscle protein metabolism in human skeletal muscle tissue during provision of overnight preoperative total parenteral nutrition (TPN). Twenty‐two patients (11/group) scheduled for upper GI surgery due to malignant or benign disease received a continuous peripheral all‐in‐one TPN infusion (30 kcal/kg/day, 0.16 gN/kg/day) or saline infusion for 12 h prior operation. Biopsies from the rectus abdominis muscle were taken at the start of operation for isolation of muscle RNA. RNA expression microarray analyses were performed with Agilent Sureprint G3, 8 × 60K arrays using one‐color labeling. 447 mRNAs were differently expressed between study and control patients (P < 0.1). mRNAs related to ribosomal biogenesis, mRNA processing, and translation were upregulated during overnight nutrition; particularly anabolic signaling S6K1 (P < 0.01–0.1). Transcripts of genes associated with lysosomal degradation showed consistently lower expression during TPN while mRNAs for ubiquitin‐mediated degradation of proteins as well as transcripts related to intracellular signaling pathways, PI3 kinase/MAPkinase, were either increased or decreased. In conclusion, muscle mRNA alterations during overnight standard TPN infusions at constant rate altered mRNAs associated with style="fixed-case">mTOR signaling; increased initiation of protein translation; and suppressed autophagy/lysosomal degradation of proteins. This indicates that overnight preoperative parenteral nutrition is effective to promote muscle protein metabolism.
机译:肌肉质量的丧失与住院患者发病率和死亡率增加的风险有关。短期人工营养对治疗效果的不确定性仍然存在,尤其是骨骼肌蛋白质平衡的改善。在这项研究中,应用算法微阵列分析来绘制与提供全天候术前全肠外营养(TPN)期间人骨骼肌组织中肌肉蛋白质代谢相关的细胞变化的图。因恶性或良性疾病而计划进行上消化道手术的22例患者(11 /组)接受了连续的外周全TPN输注(30 kcal / kg /天,0.16 gN / kg /天)或生理盐水输注事先手术12小时。在手术开始时从腹直肌进行活检以分离肌肉RNA。 RNA表达微阵列分析是使用Agilent Sureprint G3 8×60K阵列进行单色标记。在研究和对照患者之间447种mRNA表达差异(P <0.1)。在过夜营养期间,与核糖体生物发生,mRNA加工和翻译有关的mRNA被上调;特别是合成代谢信号转导S6K1(P <0.01-0.1)。与溶酶体降解相关的基因转录物在TPN期间始终表达较低,而泛素介导的蛋白质降解的mRNA和与细胞内信号通路相关的转录物PI3激酶/ MAP激酶则升高或降低。总之,过夜标准TPN输注期间肌肉mRNA的变化以恒定速率改变了与 style =“ fixed-case”> mTOR 信号相关的mRNA。增加蛋白质翻译的启动;并抑制蛋白质的自噬/溶酶体降解。这表明术前通宵的肠胃外营养可有效促进肌肉蛋白质代谢。

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