不同证型更年期综合征妇女血浆UPLC-QTOF/MS代谢组学特征研究

摘要

Objective It is to study UPLC-QTOF/MS metabolomic characteristics of climacteric women with deficiency of kidney Yin,stagnation of liver Qi,and deficiency of liver-kidney Yin pattern,and to explore the application of UPLC-QTOF/MS metabonomics in research of syndrome pattern classification on climacteric syndrome.Methods Plasma samples from 25 climacteric women with deficiency of kidney Yin,stagnation of liver Qi,and deficiency of liver-kidney Yin patterns,as well as healthy age-matched women were determined by UPLC-QTOF/MS respectively.The model of OPLS-DA was established to explore the differences of plasma metabolite profiling of climacteric women with different syndrome patterns,and to find potential biomarkers.Results OPLS-DA showed that metabolite profiling based on UPLC-QTOF/MS of climacteric women with different syndrome patterns could be clearly classified,and there existed 16 potential biomarkers including amino acids,fatty acids,phospholipids,carbohydrates,esters and alcohols which showed significant differences among three groups.Compared with the healthy age-matched women,the contents of 3 kinds of amino acids,8 kinds of fatty acids and organic acids,one kind of phospholipid,alcohol,ester,ketone and carbohydrate showed significant differences among climacteric women with different syndrome patterns (P<0.05),which suggested that climacteric women with different syndrome patterns occurred metabolic disorders of amino acids,fatty acids,phospholipids,energy and carbohydrate.Conclusion The metabolite profiling based on UPLC-QTOF/MS of climacteric women with different syndrome patterns showed significant differences,so we could determine the specific biomarkers by metabolomic analysis,and classify climacteric syndrome with different syndrome patterns to some extent.%目的 研究肾阴虚型、肝气郁结型及肝肾阴虚型更年期综合征妇女血浆超高效液相色谱-四极杆飞行时间串联质谱(UPLC-QTOF/MS)代谢组学特征,探讨UPLC-QTOF/MS代谢组学技术在妇女更年期综合征中医分型中的应用价值.方法 对肾阴虚型、肝气郁结型、肝肾阴虚型更年期综合征妇女及健康同龄妇女各25例的血浆样品进行UPLC-QTOF/MS检测,建立正交偏最小二乘法判别分析(OPLS-DA)模型,比较不同证型更年期综合征妇女血浆代谢物谱的差异,寻找潜在的生物标志物.结果 OPLS-DA分析表明,不同证型更年期综合征及健康同龄妇女血浆UPLC-QTOF/MS代谢物谱能够被明确区分,鉴定出包括氨基酸、脂肪酸、磷脂、糖类、酯类以及醇类等16个潜在生物标志物在3组中存在明显差异.与健康同龄妇女相比,不同证型更年期妇女血浆内3种氨基酸含量异常(P<0.05),8种脂肪酸及有机酸类含量异常(P<0.05),磷脂、醇类、酯类、酮体及糖类各1种含量异常(P<0.05),不同证型更年期妇女发生明显氨基酸代谢、脂肪酸代谢、磷脂代谢、能量代谢以及糖代谢等代谢紊乱.结论 不同证型更年期综合征妇女血浆UPLC-QTOF/MS代谢物谱存在显著差异,能从代谢组学分析中确定其特异生物标志物,据此在一定程度上区分更年期综合征的不同中医证型.