湿热发黄证之乙型肝炎病毒相关慢加急性肝衰竭不同分期的生物标志物筛查

Screening for biomarkers in different stages of HBV-related acute-on-chronic liver failure in damp-heat and yellowish syndrome

目的通过对湿热发黄证之乙型肝炎病毒相关慢加急性肝衰竭(HBV-related acute-on-chronic liver failure,HBVACLF)不同分期(早、中和晚期)的人血清样本进行代谢组学轮廓分析,分析其相关性与差异,并从中筛选具有差异性的小分子代谢物,即生物标志物。方法湿热发黄证HBV-ACLF样本27例,其中早期14例,中期6例,晚期7例,运用高效液相色谱-四级杆飞行时间串联质谱仪技术检测3个不同分期血清样本中的小分子代谢产物,通过Data Analysis和Mzmine软件进行色谱峰识别后进行偏最小二乘法-判别分析,找出潜在生物标志物。结果共筛选出8个生物标志物;湿热发黄证之HBV-ACLF患者早、中、晚期之间具有明显的代谢组学差异,小分子代谢物也发生了显著性变化。结论影响湿热发黄证HBV-ACLF不同分期的生物标志物种类有视黄醇维生素类物质、前列腺素类物质、环氧脂肪酸、甾体类激素、甘油三酯类物质、甘油双酯类物质、磷脂酰乙醇胺类物质、甲状腺素葡萄糖苷酸。

Objective To analyze the correlation and difference in the serum samples of patients in different stages（ early,middle and late stages） of HBV-related acute-on-chronic liver failure（ HBV-ACLF） in damp-heat and yellowish syndrome by metabonomics contour analysis,and select the small-molecule metabolites with the otherness,namely,biomarkers. Methods 27 samples of HBVACLF of damp-heat and yellowish syndrome were included including 14 samples in early stage,6 samples in middle stage and 7samples in late stage. HPLC-Q-TOF-MS / MS was used to detect the small-molecule metabolites of serum samples in three different stages. PLS-DA was carried out after the chromatographic peak recognition by the use of Data Analysis and Mzmine software to find the potential biomarkers. Results A total of eight biomarkers were selected. There existed obvious difference in HBV-ACLF patients of damp-heat and yellowish syndrome in early,middle and late stages,as well as there appeared significant changes in small-molecule metabolites. Conclusion The biomarkers to affect different stages of HBV-ACLF in damp-heat and yellowish syndrome include retinol vitamins,prostaglandins, epoxy fatty acid, steroids hormone, triglycerides, glycerin diesters, phosphatidyl ethanolamine, and thyroxine glucoside acid.