Thorne Adam M, Huang Honglei, O'Brien Darragh P, Eijken Marco, Krogstrup Nicoline Valentina, Norregaard Rikke, Møller Bjarne, Ploeg Rutger J, Jespersen Bente, Kessler Benedikt M
Nuffield Department of Surgical Sciences and Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Clin Proteomics. 2020 Nov 2;17(1):39. doi: 10.1186/s12014-020-09301-x.
Remote ischaemic conditioning (RIC) is currently being explored as a non-invasive method to attenuate ischaemia/reperfusion injuries in organs. A randomised clinical study (CONTEXT) evaluated the effects of RIC compared to non-RIC controls in human kidney transplants.
RIC was induced prior to kidney reperfusion by episodes of obstruction to arterial flow in the leg opposite the transplant using a tourniquet (4 × 5 min). Although RIC did not lead to clinical improvement of transplant outcomes, we explored whether RIC induced molecular changes through precision analysis of CONTEXT recipient plasma and kidney tissue samples by high-resolution tandem mass spectrometry (MS/MS).
We observed an accumulation of muscle derived proteins and altered amino acid metabolism in kidney tissue proteomes, likely provoked by RIC, which was not reflected in plasma. In addition, MS/MS analysis demonstrated transient upregulation of several acute phase response proteins (SAA1, SAA2, CRP) in plasma, 1 and 5 days post-transplant in RIC and non-RIC conditions with a variable effect on the magnitude of acute inflammation.
Together, our results indicate sub-clinical systemic and organ-localised effects of RIC.
远程缺血预处理（RIC）目前正作为一种减轻器官缺血/再灌注损伤的非侵入性方法进行研究。一项随机临床研究（CONTEXT）评估了在人类肾移植中RIC与非RIC对照相比的效果。
在肾再灌注前，使用止血带对移植对侧腿部的动脉血流进行阻断（4×5分钟）来诱导RIC。尽管RIC并未导致移植结果的临床改善，但我们通过高分辨率串联质谱（MS/MS）对CONTEXT受者的血浆和肾组织样本进行精确分析，探讨RIC是否诱导了分子变化。
我们观察到肾组织蛋白质组中肌肉衍生蛋白的积累和氨基酸代谢的改变，这可能是由RIC引起的，而血浆中未体现这一点。此外，MS/MS分析表明，在移植后1天和5天，RIC组和非RIC组血浆中几种急性期反应蛋白（SAA1、SAA2、CRP）出现短暂上调，对急性炎症程度的影响各不相同。
总之，我们的结果表明RIC具有亚临床全身和器官局部效应。
