摘要
目的通过液相色谱质谱联用的代谢组学方法,分析与原发性肾病综合征(PNS)相关的异常代谢通路,探讨PNS的发病机制。方法应用超高效液相色谱-高分辨质谱法方法对40例PNS患者(观察组)和40例健康体检者(对照组)血清样本中的代谢物进行检测,采用正交偏最小二乘判别分析(OPLS-DA)法进行模式识别,构建PNS诊断模型,采用Met PA数据库进行代谢通路分析。结果 OPLS-DA模型的质量参数R2X=71.4%,Q2Y=0.517,观察组、对照组间的区分非常明显。代谢通路分析共筛选出有差异的代谢物相关通路9个,其中硫胺素代谢、嘧啶代谢、苯基丙氨酸代谢、柠檬酸循环4个代谢通路影响值均大于0.1。结论 PNS患者存在硫胺素代谢、嘧啶代谢、苯基丙氨酸代谢、柠檬酸循环代谢紊乱,可能与PNS的发生发展密切相关。
Objective To analyze the disturbed metabolic pathways associated with primary nephrotic syndrome（ PNS） by liquid chromatography/mass spectrometry metabolomics method in order to explore the pathogenesis. Methods Ultraperformance liquid chromatography tandem quadrupole Q Exactive-Orbitrap high resolution mass spectrometry（ UPLCQ Exactive HRMS） method was used in 40 cases of PNS patients and 40 serum samples from healthy physical examination people to detect metabolites. The orthogonal partial least squares-discriminant analysis（ OPLS-DA） was employed to study the metabolomics differences between control group and PNS patients group. A disease-specific metabolic diagnosis model was established,and metabolic pathway analysis was performed by using Met PA database. Results A OPLS-DA model（ R2 X = 71. 4%,Q2 Y = 0. 517） was constructed with satisfactory discriminating ability to separate PNS patients and control groups. There were 9 disturbed pathways involved in PNS patients,of which thiamine metabolism,pyrimidine metabolism,phenylalanine metabolism and citric acid cycle metabolic pathways＇ influence values were greater than 0. 1. Conclusions There are metabolic disorders of phenylalanine metabolism,thiamine metabolism,citric acid cycle metabolism and pyrimidine metabolism,which may be closely related to the occurrence and development of PNS.
出处
《山东医药》
CAS
北大核心
2016年第30期1-4,I0001,共5页
Shandong Medical Journal
基金
国家自然科学基金资助项目(81102684)
关键词
代谢组学
液相色谱质谱联用
原发性肾病综合征
代谢通路
通路分析
metabolomics
liquid chromatography mass spectrometry
primary nephrotic syndrome
metabolic pathway
pathway analysis
