多囊卵巢综合征痰湿证患者血清代谢组学分析及其生物标志物筛选

摘要

目的：应用基于核磁共振的代谢组学方法研究多囊卵巢综合征（ PCOS）痰湿证患者和健康人的血清代谢物的差异，探讨与PCOS痰湿证相关的生物标志物及其发病机制。方法对收集到的PCOS痰湿证患者、健康人临床血清样本进行核磁共振氢谱预处理，随后使用SIMCA-P＋软件进行模式识别多变量分析。经主成分分析法、偏最小二乘法-判别分析方法分析数据后，再经正交偏最小二乘法-判别分析进行修正，通过分析组间的差异代谢成分，最终筛选鉴定出PCOS痰湿证的生物标志物。结果 PCOS痰湿证患者和健康人之间的血清代谢成分存在差异。 PCOS痰湿证患者较健康人血清中降低的代谢物有1-甲基组氨酸、柠檬酸、乙醇、甘油磷酸胆碱、低密度脂蛋白L1、脂质L6（ P＜0．05），增加的有乙酰乙酸、极低密度脂蛋白L5、脂质L7、乳酸、赖氨酸、N-乙酰糖蛋白、苏氨酸（ P＜0．05）。结论上述13种代谢物可能是PCOS痰湿证潜在的生物标志物。 PCOS痰湿证患者血清代谢组分的变化机制和三羧酸循环、糖代谢、脂代谢和氨基酸代谢密切相关，主要表现为三羧酸循环障碍、糖代谢缓慢、脂肪动员加强。%Objective To study the differences in the serum metabolites for polycystic ovary syndrome ( PCOS) be-tween patients with phlegm-dampness syndrome and healthy people with the application of metabonomics based on nuclear magnetic resonance ( NMR) , and to investigate the biomarkers associated with phlegm-dampness syndrome of PCOS as well as the mechanism .Methods After the preparation of clinical serum samples collected from PCOS patients with phlegm-dampness syndrome ( phlegm-dampness syndrome group , n=20 ) and the healthy people ( control group , n=20 ) , we pre-processed the hydrogen spectrum for nuclear magnetic resonance , then using SIMCA-P+software for pattern recognition of multivariate analysis .After the data were analyzed by the principal component analysis ( PCA ) and partial least squares discriminant analysis ( PLS-DA ) , then they were amended by the orthogonal partial least squares discriminant analysis ( OPLS-DA) .According to the analysis of different metabolic components , the biomarkers of phlegm-dampness syndrome of PCOS were finally screened and identified .Results There were significant differences in the serum metabolites between the phlegm-dampness syndrome group and the control group .The levels of 1-methyl histidine, citrate, ethanol, glycerol phosphate choline, low density lipoprotein L1 and lipid L6 were lower in the phlegm-dampness syndrome group as compared with those of the control group, and statistically significant difference was found (all P<0.05).And the levels of acetoac-etate, very low density lipoprotein L5, lipid L7, lactate, lysine, n-acetyl glycoprotein and threonine were higher in the phlegm-dampness syndrome group as compared with those of the control group , and statistically significant difference was found between the two groups (all P<0.05).Conclusions These 13 metabolites could be the potential biomarkers for P-COS patients with phlegm-dampness syndrome .The change mechanism of serum metabolites in PCOS patients was closely related with the tricarboxylic acid cycle , glucose metabolism , lipid metabolism and protein metabolism , which mainly mani-fested the disorders of tricarboxylic acid cycle , slowed glucose metabolism and increased lipid and protein metabolism .