Gastrointestinal Surgery, Nottingham Digestive Diseases Centre, National Institute of Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals and University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK.
MRC/ARUK Centre for Musculoskeletal Ageing Research, National Institute of Health Research (NIHR) Nottingham Biomedical Research Centre, School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK.
Clin Nutr. 2018 Dec;37(6 Pt A):2178-2185. doi: 10.1016/j.clnu.2017.10.020. Epub 2017 Nov 2.
BACKGROUND & AIMS: Postoperative hyperglycaemia is common in patients having major surgery and is associated with adverse outcomes. This study aimed to determine whether bacteraemia contributed to postoperative systemic inflammation, and whether increases in the expression of muscle mRNAs and proteins reflecting increased muscle inflammation, atrophy and impaired carbohydrate oxidation were evident at the time of surgery, and both local and distant to the site of trauma, and could be associated with impaired glucoregulation.
Fifteen adult patients without diabetes undergoing major abdominal surgery participated in this observational study set in a university teaching hospital. Arterialised-venous blood samples and muscle biopsies were obtained before and after major elective abdominal surgery, from sites local (rectus abdominis - RA) and remote to the site of surgery (vastus lateralis - VL). The main outcome measures included blood glucose concentrations, gut permeability and changes in expression of muscle mRNAs and proteins linked to inflammation and glucose regulation.
Immediately postoperatively, RA demonstrated markedly increased mRNA expression levels of cathepsin-L (7.5-fold, P < 0.05), FOXO1 (10.5-fold, P < 0.05), MAFbx (11.5-fold, P < 0.01), PDK4 (7.8-fold, P < 0.05), TNF-α (16.5-fold, P < 0.05) and IL-6 (1058-fold, P < 0.001). A similar, albeit blunted, response was observed in VL. Surgery also increased expression of proteins linked to inflammation (IL-6; 6-fold, P < 0.01), protein degradation (MAFbx; 4.5-fold, P < 0.5), and blunted carbohydrate oxidation (PDK4; 4-fold, P < 0.05) in RA but not VL. Increased systemic inflammation (TNF-α, P < 0.05; IL-6, P < 0.001), and impaired postoperative glucose tolerance (P < 0.001), but not bacteraemia (although gut permeability was increased significantly, P < 0.05) or increased plasma cortisol, were noted 48 h postoperatively.
A systemic postoperative proinflammatory response was accompanied by muscle inflammation and metabolic dysregulation both local and remote to the site of surgery, and was not accompanied by bacteraemia.
Registered at http://clinicaltrials.gov (NCT01134809).
术后高血糖在接受重大手术的患者中很常见，并且与不良结局相关。本研究旨在确定菌血症是否导致术后全身炎症，以及在手术时，即在创伤部位附近和远处，肌肉 mRNA 和反映肌肉炎症、萎缩和糖氧化受损的蛋白质表达是否增加，并且是否与糖调节受损有关。
本观察性研究在一所大学教学医院进行，纳入了 15 名无糖尿病的成年患者，他们接受了重大腹部手术。在择期大腹部手术后，从手术部位（腹直肌-RA）和手术部位以外的部位（股外侧肌-VL）采集动脉化静脉血样本和肌肉活检。主要观察指标包括血糖浓度、肠道通透性以及与炎症和葡萄糖调节相关的肌肉 mRNA 和蛋白质表达的变化。
术后即刻，RA 的组织蛋白酶-L（7.5 倍，P<0.05）、FOXO1（10.5 倍，P<0.05）、MAFbx（11.5 倍，P<0.01）、PDK4（7.8 倍，P<0.05）、TNF-α（16.5 倍，P<0.05）和 IL-6（1058 倍，P<0.001）的 mRNA 表达水平显著增加。VL 也观察到类似但减弱的反应。手术还增加了 RA 中与炎症相关的蛋白质（IL-6；6 倍，P<0.01）、蛋白质降解（MAFbx；4.5 倍，P<0.5）和碳水化合物氧化受损（PDK4；4 倍，P<0.05）的表达，但 VL 中没有。术后 48 小时观察到全身炎症增加（TNF-α，P<0.05；IL-6，P<0.001）和术后葡萄糖耐量受损（P<0.001），但未观察到菌血症（尽管血浆皮质醇显著增加，P<0.05）。
手术后全身促炎反应伴有肌肉炎症和代谢失调，不仅在手术部位附近，而且在手术部位以外，并且与菌血症无关。
在 http://clinicaltrials.gov 注册（NCT01134809）。
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