液相色谱-质谱联用系统在肝硬化不同阶段代谢轮廓研究中的应用

采用高效液相色谱-轨道离子阱质谱联用(HPLC-LTQ Orbitrap XL MS)代谢组学研究平台分析不同阶段肝硬化病人和健康人群的血清标本,获取代谢轮廓。采用模式识别方法结合非参数检验对数据进行分析。研究发现,由肝硬化A级组、B级组、C级组和健康对照组的代谢轮廓构建的正交偏最小二乘判别分析(OPLS-DA)模型(R2（Y）=90.1%, Q2=66.7%),对检测组数据的预测准确率达到93.8%,具有很好的判别能力。从代谢轮廓中可以鉴别出用于区分不同疾病阶段的特异性代谢标志物,如溶血磷脂酰胆碱、甘氨鹅去氧胆酸、半胱氨酸、甘氨酸、氨基己二酸、哌可酸等。研究结果表明: 利用代谢组学方法获得的血清代谢轮廓可以用来构建区分模型和寻找代谢标志物,为乙肝肝硬化的诊断和监测提供支持和依据。

Application of liquid chromatography-mass spectrometry in the study of metabolic profiling of cirrhosis in different grades

The metabolic profiles were obtained by high performance liquid chromatography combined with a LTQ Orbitrap XL mass spectrometer (HPLC-LTQ Orbitrap XL MS) platform to analyze serum specimens from the people of healthy control group and patients of hepatitis B virus (HBV)-induced cirrhosis. Then the data were analyzed with the pattern recognition methods and nonparametric test. The orthogonal partial least squares-discriminant analysis (OPLS-DA) mode (R2（Y）=90.1%, Q2=66.7%) was constructed by the serum metabolic profiles of Child-Pugh grades A, B, C groups and a healthy control group in the training set and the good discrimination ability of this mode for the testing set was demonstrated with the accuracy of 93.8%. The corresponding specific metabolic biomarkers used to distinguish different cirrhosis grades were discovered, such as lysophosphatidylcholine (LPC), glycolchenodeoxycholic acid (GCDCA), cysteine, glycine, aminoadipic acid, pipecolic acid. The results suggest that the metabolic profiling of serum can be used to construct the discrimination mode and discover the metabolic biomarkers for the HBV-induced cirrhosis, which will support the diagnosis and evaluation of the HBV-induced cirrhosis.