重大择期手术后皮肤围术期氧输送的蛋白质组学特征：一项随机对照试验的机制子研究。

Proteomic signatures for perioperative oxygen delivery in skin after major elective surgery: mechanistic sub-study of a randomised controlled trial.

机构信息

Translational Mass Spectrometry Research Group, UCL Institute of Child Health, London, UK.

Translational Medicine & Therapeutics, William Harvey Research Institute, Queen Mary University of London, London, UK.

出版信息

Br J Anaesth. 2021 Oct;127(4):511-520. doi: 10.1016/j.bja.2021.06.003. Epub 2021 Jul 6.

DOI:10.1016/j.bja.2021.06.003

PMID:34238546

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8524389/

Abstract

BACKGROUND

Maintaining adequate oxygen delivery (DO) after major surgery is associated with minimising organ dysfunction. Skin is particularly vulnerable to reduced DO. We tested the hypothesis that reduced perioperative DO fuels inflammation in metabolically compromised skin after major surgery.

METHODS

Participants undergoing elective oesophagectomy were randomised immediately after surgery to standard of care or haemodynamic therapy to achieve their individualised preoperative DO. Abdominal punch skin biopsies were snap-frozen before and 48 h after surgery. On-line two-dimensional liquid chromatography and ultra-high-definition label-free mass spectrometry was used to characterise the skin proteome. The primary outcome was proteomic changes compared between normal (≥preoperative value before induction of anaesthesia) and low DO (<preoperative value before induction of anaesthesia) after surgery. Secondary outcomes were functional enrichment analysis of up/down-regulated proteins (Ingenuity pathway analysis; STRING Protein-Protein Interaction Networks). Immunohistochemistry and immunoblotting confirmed selected proteomic findings in skin biopsies obtained from patients after hepatic resection.

RESULTS

Paired punch skin biopsies were obtained from 35 participants (mean age: 68 yr; 31% female), of whom 17 underwent oesophagectomy. There were 14/2096 proteins associated with normal (n=10) vs low (n=7) DO after oesophagectomy. Failure to maintain preoperative DO was associated with upregulation of proteins counteracting oxidative stress. Normal DO after surgery was associated with pathways involving leucocyte recruitment and upregulation of an antimicrobial peptidoglycan recognition protein. Immunohistochemistry (n=6 patients) and immunoblots after liver resection (n=12 patients) supported the proteomic findings.

CONCLUSIONS

Proteomic profiles in serial skin biopsies identified organ-protective mechanisms associated with normal DO after major surgery.

CLINICAL TRIAL REGISTRATION

ISRCTN76894700.

摘要

背景

术后维持足够的氧输送（DO）与最小化器官功能障碍有关。皮肤特别容易受到 DO 降低的影响。我们检验了一个假说，即术后代谢受损的皮肤中的 DO 减少会引发炎症。

方法

择期接受食管切除术的患者在手术后立即随机分配到标准治疗或血流动力学治疗，以达到他们术前的个体化 DO。在手术前和手术后 48 小时，进行腹部皮肤活检。在线二维液相色谱和超高分辨率无标记质谱用于分析皮肤蛋白质组。主要结局是与术后正常（≥麻醉诱导前的术前值）和低 DO（<麻醉诱导前的术前值）相比，蛋白质组的变化。次要结局是对上调/下调蛋白进行功能富集分析（Ingenuity 通路分析；STRING 蛋白质-蛋白质相互作用网络）。免疫组织化学和免疫印迹证实了从接受肝切除术的患者皮肤活检中获得的部分蛋白质组学发现。

结果

从 35 名参与者（平均年龄：68 岁；31%为女性）中获得了配对的皮肤活检，其中 17 名接受了食管切除术。在食管切除术后，有 14/2096 种蛋白质与正常 DO（n=10）和低 DO（n=7）相关。术前 DO 维持失败与对抗氧化应激的蛋白质上调有关。术后正常 DO 与涉及白细胞募集和上调抗菌肽聚糖识别蛋白的途径有关。免疫组织化学（n=6 例患者）和肝切除术后免疫印迹（n=12 例患者）支持蛋白质组学发现。