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Metabonomics study of the acute graft rejection in rat renal transplantation using reversed-phase liquid chromatography and hydrophilic interaction chromatography coupled with mass spectrometry

机译：metabonomics study of the acute graft rejection in rat renal transplantation using reversed-phase liquid chromatography and hydrophilic interaction chromatography coupled with mass spectrometry

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摘要

Acute graft rejection is one of the most common and serious post complications in renal transplantation, noninvasive diagnosis of acute graft rejection is essential for reducing risk of surgery and timely treatment. In this study, a non-targeted metabonomics approach based on ultra performance liquid chromatography (UPLC) coupled with quadrupole time-of-flight mass spectrometry (MS) is used to investigate the effect of acute graft rejection in rat renal transplantation on metabolism. To collect more metabolite information both hydrophilic interaction chromatography and reversed-phase liquid chromatography were used. Using the partial least squares-discriminant analysis, we found that the change of metabonome in a sham-operated group and a non-graft rejection group had a similar trend, while that of the acute graft rejection group was clearly different. Several discriminating metabolites of the acute graft rejection were identified, including creatinine, phosphatidyl-cholines, lyso-phosphatidylcholines, carnitine C16:0, free fatty acids and indoxyl sulfate etc. These discriminating metabolites suggested that acute graft rejection in renal transplantation can lead to the accumulation of creatinine in the body, and also the abnormal metabolism of phospholipids. These findings are useful to understand the mechanisms of the rejection, it also means that a UPLC-MS metabonomic approach is a suitable tool to investigate the metabolic abnormality in the acute graft rejection in renal transplantation.
机译：急性移植排斥反应是肾移植中最常见，最严重的并发症之一，急性移植排斥反应的非侵入性诊断对于降低手术风险和及时治疗至关重要。在这项研究中，基于超高效液相色谱（UPLC）结合四极杆飞行时间质谱（MS）的非靶向代谢组学方法用于研究大鼠肾移植急性排斥反应对代谢的影响。为了收集更多的代谢物信息，使用了亲水相互作用色谱法和反相液相色谱法。使用偏最小二乘判别分析，我们发现假手术组和非移植排斥组的代谢组变化具有相似的趋势，而急性移植排斥组的代谢组变化明显。鉴定了几种急性移植排斥反应的区别代谢物，包括肌酐，磷脂酰胆碱，溶血磷脂酰胆碱，肉碱C16：0，游离脂肪酸和吲哚硫酸盐等。这些区别代谢物提示肾移植急性排斥反应可导致肾移植的急性排斥反应。肌酸酐在体内的积累，以及磷脂的异常代谢。这些发现有助于理解排斥反应的机制，也意味着UPLC-MS代谢组学方法是研究肾移植急性移植排斥反应中代谢异常的合适工具。

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