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Subclinical effects of remote ischaemic conditioning in human kidney transplants revealed by quantitative proteomics

机译:定量蛋白质组学揭示人肾移植术中远程缺血调理的亚临床效应

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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.
机译:远程缺血处理(RIC),目前正在探索作为一种非侵入性的方法来在衰减器官缺血/再灌注损伤。随机临床研究(上下文)评估RIC相比,在人类肾移植非RIC控制效果。 RIC被阻塞发作在腿动脉血流使用止血带(4?×→5→min),将移植肾相反再灌注前诱导。虽然RIC没有导致临床改善移植结果,我们探讨是否RIC诱导通过高分辨率的串联质谱(MS / MS)上下文收件人血浆和肾组织样本的精度分析分子变化。我们观察到肌肉衍生的蛋白质的积累和改变在肾组织蛋白质组氨基酸代谢,可能是由R​​IC引起,这是不反映在等离子体。此外,MS / MS分析证实在等离子体几个急性期反应蛋白(SAA1,SAA2,CRP)的瞬态上调,1和5?天移植后在RIC和非RIC条件与急性的大小的可变效果炎。总之,我们的结果表明RIC的亚临床系统性和器官的局部效应。

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