基于超高效液相色谱-四级杆飞行时间质谱技术的急性百草枯中毒患者早期血浆代谢组学研究  

Plasma Metabolomics Study of Patients with Acute Paraquat Poisoning in Early Stage Based on UPLC-QTOF-MS

作　　者：杨娜[1] 张天祺 蒋陈晓 罗雪梅[1] 朱怀军[1] 王敏[1] YANG Na;ZHANG Tianqi;JIANG Chenxiao;LUO Xuemei;ZHU Huaijun;WANG Min(Department of Pharmacy,Affiliated of Medical School,Nanjing University,Nanjing 210008,China;Department of Emergency,Nanjing Drum Tower Hospital,Affiliated of Medical School,Nanjing University,Nanjing 210008,China)

机构地区：[1]南京大学医学院附属鼓楼医院药学部,南京210008 [2]南京大学医学院附属鼓楼医院急诊医学科,南京210008

出　　处：《医药导报》2023年第9期1291-1298,共8页Herald of Medicine

基　　金：国家自然科学基金资助项目(82204501);江苏省自然科学基金资助项目(BK20190122)。

摘　　要：目的采用代谢组学技术检测急性百草枯中毒患者早期血浆差异代谢物,寻找用于百草枯急性中毒预后评估的重要生物标志物和潜在干预靶点。方法基于超高效液相色谱-四级杆飞行时间质谱(UPLC-QTOF-MS)技术,收集百草枯中毒患者与健康人各12例血浆样本,进行对比分析,采用多元统计方法筛选差异化合物,进一步分析候选代谢物在中毒后存活及死亡患者中水平的差异性。结果中毒患者较健康人群共筛选得到包含磷脂、氨基酸、饱和或不饱和脂肪酸等48种差异代谢物。其中,溶血磷脂酰乙醇胺(LysoPE,22:6)和溶血磷脂酰胆碱(LysoPC,20:1)变化最为显著,中毒患者血浆水平分别为健康人的16.2倍(P<0.05)和17.9倍(P<0.05)。中毒后死亡患者血浆中LysoPE、LysoPC、L-乳酸、二十碳二烯酸、4-羟丁酸等7种代谢物水平显著高于存活者(P<0.05)。其中,LysoPE(22:6)和LysoPC(20:1)变化同样最为显著。此外,中毒后死亡患者血浆中苯丙氨酰苯丙氨酸水平显著低于存活者(P<0.01)。结论溶血磷脂酰乙醇胺和溶血磷脂等代谢物可能参与了百草枯中毒损伤的病理进程,其对于急性百草枯中毒预后评估具有潜在应用价值。Objective To explore early plasma differential metabolites in patients with acute paraquat poisoning based on the metabolomics approach,and to find the important biomarkers for the prognosis evaluation and the therapeutic targets.Methods Plasma samples of 12 patients with paraquat poisoning and 12 healthy people were analyzed using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry(UPLC-QTOF-MS).Plasma differential metabolites between paraquat poisoning patients and healthy controls were screened by multivariate statistical method,and their levels in the death and survival subgroups of paraquat poisoning patients were further analyzed.Results A total of 48 differential metabolites,including phospholipids,amino acids,and saturated or unsaturated fatty acids,were screened in the poisoned patients compared to the healthy controls.Among them,the plasma levels of LysoPE(22:6)and LysoPC(20:1)showed the most significant changes in the poisoned patients,which were 16.2 times(P<0.05)and 17.9 times(P<0.05)higher than those in the healthy controls,respectively.Plasma levels of seven metabolites,including LysoPE,LysoPC,L-lactic acid,eicosadienic acid,and 4-hydroxybutyric acid were significantly higher in the patients who died after poisoning than in the surviving patients(P<0.05).LysoPE(22:6)and LysoPC(20:1)similarly varied most significantly.In addition,plasma phenyl alanyl phenylalanine level was significantly lower in the patients who died after poisoning than in the surviving patients(P<0.01).Conclusion Those screened metabolites may participate in the pathological process of paraquat poisoning injury and may have potential application value for the prognosis evaluation.

关 键 词：百草枯 超高效液相色谱-四级杆飞行时间质谱 代谢组学 磷脂 脂肪酸 

分 类 号：R595.4[医药卫生—内科学] R969.1[医药卫生—临床医学]