Wolfer Arnaud M, Scott Alasdair J, Rueb Claudia, Gaudin Mathieu, Darzi Ara, Nicholson Jeremy K, Holmes Elaine, Kinross James M
Division of Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London, London, UK.
Imperial College Healthcare NHS Trust, London, UK.
J Transl Med. 2017 Apr 26;15(1):83. doi: 10.1186/s12967-017-1171-2.
Oxylipins are potent lipid mediators demonstrated to initiate and regulate inflammation yet little is known regarding their involvement in the response to surgical trauma. As key modulators of the inflammatory response, oxylipins have the potential to provide novel insights into the physiological response to surgery and the pathophysiology of post-operative complications. We aimed to investigate the effects of major surgery on longitudinal oxylipin profile.
Adults patients undergoing elective laparoscopic or open colorectal resections were included. Primary outcomes were serum oxylipin profile quantified by ultra high-performance liquid chromatography-mass spectrometry, serum white cell count and C-reactive protein concentration. Serum samples were taken at three time-points: pre-operative (day zero), early post-operative (day one) and late post-operative (day four/five).
Some 55 patients were included, of which 33 (60%) underwent surgery that was completed laparoscopically. Pre-operative oxylipin profiles were characterised by marked heterogeneity but surgery induced a common shift resulting in more homogeneity at the early post-operative time-point. By the late post-operative phase, oxylipin profiles were again highly variable. This evolution was driven by time-dependent changes in specific oxylipins. Notably, the levels of several oxylipins with anti-inflammatory properties (15-HETE and four regioisomers of DHET) were reduced at the early post-operative point before returning to baseline by the late post-operative period. In addition, levels of the pro-inflammatory 11-HETE rose in the early post-operative phase while levels of anti-thrombotic mediators (9-HODE and 13-HODE) fell; concentrations of all three oxylipins then remained fairly static from early to late post-operative phases. Compared to those undergoing laparoscopic surgery, patients undergoing open surgery had lower levels of some anti-inflammatory oxylipins (8,9-DHET and 17-HDoHE) in addition to reduced concentrations of anti-thrombotic mediators (9-HODE and 13-HODE) with increased concentration of their pro-thrombotic counterpart (TxB2).
Serum oxylipin profile is modified by surgical intervention and may even be sensitive to the degree of surgical trauma and therefore represents a novel descriptor of the surgical systemic inflammatory response.
氧化脂质是强效脂质介质，已证实其可引发和调节炎症，但关于其在手术创伤反应中的作用知之甚少。作为炎症反应的关键调节因子，氧化脂质有可能为手术的生理反应及术后并发症的病理生理学提供新的见解。我们旨在研究大手术对氧化脂质纵向变化情况的影响。
纳入接受择期腹腔镜或开放结直肠切除术的成年患者。主要观察指标为通过超高效液相色谱 - 质谱法定量的血清氧化脂质变化情况、血清白细胞计数及C反应蛋白浓度。在三个时间点采集血清样本：术前（第0天）、术后早期（第1天）和术后晚期（第4/5天）。
共纳入约55例患者，其中33例（60%）接受了腹腔镜下完成的手术。术前氧化脂质变化情况具有显著异质性，但手术导致了一种共同变化，使术后早期时间点的同质性更高。到术后晚期，氧化脂质变化情况再次高度可变。这种演变是由特定氧化脂质的时间依赖性变化驱动的。值得注意的是，几种具有抗炎特性的氧化脂质（15 - HETE和DHET的四种区域异构体）的水平在术后早期降低，然后在术后晚期恢复到基线水平。此外，促炎的11 - HETE水平在术后早期升高，而抗血栓介质（9 - HODE和13 - HODE）水平下降；这三种氧化脂质的浓度从术后早期到晚期基本保持稳定。与接受腹腔镜手术的患者相比，接受开放手术的患者除了抗血栓介质（9 - HODE和13 - HODE）浓度降低且其促血栓对应物（TxB2）浓度升高外，一些抗炎氧化脂质（8,9 - DHET和17 - HDoHE）水平也较低。
血清氧化脂质变化情况会因手术干预而改变，甚至可能对手术创伤程度敏感，因此代表了手术全身炎症反应的一种新描述指标。
