非酒精性脂腑性肝病患者血清脂质组学研究

A serum lipidomic study of patients with non-alcoholic fatty liver disease

目的通过对非酒精性脂肪性肝病（NAFLD）患者血清脂质组学的分析，研究NAFLD的脂质代谢特征。方法受试者分为对照组（n=23）、经肝脏病理学证实的NAFLD患者组（n=42），应用超高效液相色谱-串联质谱（UPLC-MS／MS）测定血清脂质组学代谢产物，构建偏最小二乘判别分析（PLS-DA）模型，结合单因素分析差异代谢脂质。对数据进行t检验以及Mann-WhitneyU检验。结果共检测239种脂质代谢产物并进行定性定量分析，构建PLS-DA模型（R2=0．753，Q2=0．456），结合单因素分析显示，NAFLD患者血清脂质代谢与对照组之间有77种脂质存在明显差异（VIP值〉1，P〈0．05）。其中包括游离脂肪酸、磷脂酰胆碱、磷脂酰乙醇胺、磷脂酰肌醇、溶血磷脂酰胆碱、溶血磷脂酰肌醇（LPI）、缩醛磷脂酰胆碱（PlsCho）、缩醛磷脂酰乙醇胺（PlsEtn）、神经酰胺（Cer）、鞘磷脂、甘油三酯（TG）等脂质。NAFLD组单不饱和脂肪酸较对照组明显升高（均值较对照组升高39％，t=-3．954，P〈0．05）；NAFLD组TG较对照组升高（均值较对照组升高36％，Z=-2．662，P〈0．01）；且以低碳数目和低不饱和键数目的TG升高为主，而高碳数目以及多不饱和键数目的TG下降；NAFLD组LPI、Cer较对照组升高（均值较对照组分别升高：223％，t=-3．858，P〈0．05；21％，t=-2．481，JP〈0．05），而多种缩醛磷脂（PlsCho、PlsEtn）在NAFLD中显著降低（均值较对照组分别下降：18％，t=3．184，P〈0．05；200／0，f=2．363，P〈0．05）。结论NAFLD血清脂质代谢轮廓与正常人有明显差异，通过NAFLD血清脂质组学的分析可进一步阐明NAFLD的脂质代谢特征。

Objective To investigate the serum lipidomic profile in patients with nonalcoholic fatty liver disease （NAFLD）, and to analyze the lipid metabolism characteristics of NAFLD. Methods The subjects were divided into control group （23 patients） and pathologically confirmed NAFLD group （42 patients）, and ultra-high-performance liquid chromatography-tandem mass spectrometry was used to measure serum lipidomic metabolites. The partial least squares-discriminant analysis （PLS-DA） model was established to analyze the differences in lipid metabolism with reference to the univariate analysis. The t-test and Mann-Whitney U test were used for data analysis. Results A total of 239 lipids were identified and qualitative and quantitative analyses were performed. The PLS-DA model （R2 = 0.753, Q2 = 0.456） and the univariate analysis showed that 77 lipids were metabolized differentially between the NAFLD group and the control group （VIP 〉 1, P 〈 0.05）, including free fatty acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, lysophosphatidylcholine, lysophosphatidylinositol （LPI）, choline plasmalogen （PlsCbo）, ethanolamine plasmalogen （PlsEtn）, ceramide （Cer）, sphingomyelin, and triglyceride （TG）. Compared with the control group, the NAFLD group had significant increases in monounsaturated fatty acids （increased by 39%, t = -3.954, P 〈 0.05） and TGs （increased by 36%, Z = -2.662, P 〈 0.05）, mainly TGs with low numbers of carbon atoms and unsaturated bonds, while there were reductions in TGs with high numbers of carbon atoms and unsaturated bonds. In addition, compared with the control group, the NAFLD group had significant increases in the levels of LPI （increased by 223%, t = -3.858, P 〈 0.05） and Cer （increased by 21%, t = -2.481, P 〈 0.05） and significant reductions in PlsCho （reduced by 18%, t = 3.184, P 〈 0.05） and PlsEtn （reduced by 20%, t = 2.363, P 〈 0.05）. Conclusion There is a significant difference in lipid metabolism profile between NAFLD patients and healthy people, and a serum lipidomic analysis of NAFLD helps to further clarify the characteristics of lipid metabolism in patients with NAFLD.