基于超高液相色谱-四级杆飞行时间质谱联用技术筛选多囊卵巢综合征患者卵泡液生物标志物

Screening of follicular fluid biomarkers in patients with polycystic ovary syndrome based on ultrahigh performance liquid chromatography quadrupole time of flight mass spectrometry

目的分析多囊卵巢综合征(PCOS)患者卵泡液代谢组差异,找寻相关生物学标志物,探讨相关代谢通路变化。方法利用超高液相色谱-四级杆飞行时间质谱联用技术(UHPLC-QTOFMS)对PCOS患者(n=7)及对照组(n=6)的卵泡液进行代谢组学分析。结果PCOS组和对照组组间代谢物分布具有差异性,共计有60种差异代谢物,其中有20种代谢物水平下降(P<0.05),40种代谢物水平增加(P<0.05),主要有氨基酸类、脂肪酸类、有机化合物、有机氧化合物等。其中24种物质为脂质类物质,9种物质为氨基酸类。此外,血清睾酮水平与脯氨酸及多种脂肪酸(包括5-羟色胺、PS(22∶0/18∶4(6Z,9Z,12Z,15Z)))、PC(P-18∶0/22∶4(7Z,10Z,13Z,16Z))、PC(15∶0/20∶2(11Z,14Z))、24-Epibrassinolide、LysoPI(18:0/0:0)具有相关性(P<0.05)。结论本研究鉴定出了60种差异代谢物,其中有1种氨基酸、5种脂肪酸与睾酮水平呈正相关;分析了在PCOS中可能发挥重要作用的2种代谢通路:性激素合成代谢和嘧啶代谢通路,可为今后PCOS的治疗、诊断提供一定的依据和治疗靶点参考。

Objective:To investigate the changes of follicular fluid metabonomics in patients with polycystic ovary syndrome(PCOS),screen the related biological markers,and explore the related metabolic pathways.Methods:The follicular fluid of PCOS patients(n=7)and control group(n=6)were analyzed by ultra-high performance liquid chromatography quadrupole time of flight mass spectrometry(UHPLC-QTOFMS).Results:There were differences in the distribution of metabolites between the PCOS group and the control group.There were a total of 60 different metabolites,of which the level of 20 metabolites decreased(P<0.05),and the level of 40 metabolites increased(P<0.05),including amino acids,fatty acids,organic compounds,organic oxygen compounds,etc.Among them,24 substances were lipid substances and 9 substances were amino acids.In addition,the serum testosterone level was correlated with proline and a variety of fatty acids(including serotonin,PS(22∶0/18∶4(6Z,9Z,12Z,15Z)),PC(P-18∶0/22∶4)(7Z,10Z,13Z,16Z)),PC(15∶0/20∶2(11Z,14Z)),24-Epibrassinolide,LysoPI(18∶0/0∶0)(P<0.05).Conclusions:Sixty differential metabolites are identified in this study.Among them,one amino acid and five fatty acids are positively correlated with testosterone levels.Two metabolic pathways that may play an important role in PCOS,i.e.sex hormone synthesis metabolism and pyrimidine metabolism pathway,were analyzed,which can provide a certain basis and treatment target reference for the treatment and diagnosis of PCOS in the future.