CAJ | 학술논문

目的通过血浆磷脂代谢分析,发现、判别肾移植急性排斥反应的血浆生物标志物以辅助临床诊断.方法选取2009年至2010年在本院行肾移植的患者33例,为术前组,术后按照是否发生急性排斥反应分为急性排斥组(n=14)和非急性排斥组(n=19),利用超高分辨率液相色谱-四级杆-飞行时间质谱串联(UPLC-qTOF-MS)分析技术建立肾移植急性排斥反应患者血浆代谢指纹图谱.采用偏最小二乘法-判别分析(PLS-DA)分析肾移植术后急性排斥反应组与非急性排斥反应组患者的代谢差异产物,同时观察肾功能指标及肾组织病理改变.结果血浆磷脂代谢分析鉴定发现17种差异性代谢产物:肌酐、各种鞘磷脂、磷脂酰乙醇胺、磷脂酰胆碱、溶血磷脂酰胆碱等,其中传统指标肌酐水平增高,其余16种代谢产物降低.结论基于UPLC-qTOF-MS代谢组学技术对肾移植患者血浆磷脂代谢分析,揭示了急性排斥反应过程中磷脂代谢变化规律:血浆磷脂酰胆碱酯解及脂肪酸β-氧化水平明显增高,免疫抑制治疗可降低磷脂酶活性,抑制磷脂酰胆碱酯解及脂肪酸β-氧化水平,有效地抑制肾移植术后急性排斥反应的发生及发展,其作为一种辅助手段,可能在肾移植急性排斥反应的早期诊断中具有应用前景.
목적 통과혈장린지대사분석,발현、판별신이식급성배척반응적혈장생물표지물이보조림상진단.방법 선취2009년지2010년재본원행신이식적환자33례,위술전조,술후안조시부발생급성배척반응분위급성배척조(n=14)화비급성배척조(n=19),이용초고분변솔액상색보-사급간-비행시간질보천련(UPLC-qTOF-MS)분석기술건립신이식급성배척반응환자혈장대사지문도보.채용편최소이승법-판별분석(PLS-DA)분석신이식술후급성배척반응조여비급성배척반응조환자적대사차이산물,동시관찰신공능지표급신조직병리개변.결과 혈장린지대사분석감정발현17충차이성대사산물:기항、각충초린지、린지선을순알、린지선담감、용혈린지선담감등,기중전통지표기항수평증고,기여16충대사산물강저.결론 기우UPLC-qTOF-MS대사조학기술대신이식환자혈장린지대사분석,게시료급성배척반응과정중린지대사변화규률:혈장린지선담감지해급지방산β-양화수평명현증고,면역억제치료가강저린지매활성,억제린지선담감지해급지방산β-양화수평,유효지억제신이식술후급성배척반응적발생급발전,기작위일충보조수단,가능재신이식급성배척반응적조기진단중구유응용전경.
Objective Plasma phospholipid metabolism analysis was employed to investigate plasma metabolic profile of acute renal graft rejection in order to find potential disease biomarkers and reveal its pathophysiological changes.Methods Selected 33 patients which did renal transplant in our hospital during 2009 to 2010,named preoperative group.14 patients were diagnosed as acute graft rejection,and 19 patients were non-acute graft rejection.Then use ultra performance liquid chromatography (UPLC) coupled with quadrupole time of flight mass spectrometry (qTOF-MS) to establish the metabolic fingerprint in those patients.The date was preprocessed with software Markerlynx,and analyzed with partial least squares discriminant analysis (PLS-DA),and data from conventional laboratory techniques were used for assessing renal function.Results In the plasma of renal transplant patients,seventeen biomarkers were discovered:creatinine,four sphingomyelins (SM),nine phosphatidylcholines (PC),three lysophosphatidylcholine (LPC).While the creatinine was increased,the others were reduced obviously.Conclutions UPLC-qTOF-MS based metabonomics can analyze the plasma phospholipid metabolism in patients with renal transplantation,reveal the law of phospholipids metabolic changes in the process of acute rejection.The levels of plasma phosphatidylcholine's esterlysis and fatty acids' β-oxidation are increased.The immunosuppressive therapy can reduce the activity of phospholipase,inhibit the level of plasma phosphatidylcholine's esterlysis and fatty acids' β-oxidation,which restraines the development of acute rejection after renal transplantation.Therefore it may be a promising new technology in diagnosing acute renal graft rejection after renal transplantation.