目的:基于高效液相色谱-四极杆飞行时间串联质谱仪(HPLC.MS/MSQ—TOF)分析糖尿病肾病(DN)维持性血透患者单次使用含糖透析液(含葡萄糖5.5mmol/L)的代谢特征。方法:对10例DN维持性血透患者采用自身对照研究,先后单次使用无糖及含糖透析液作为无糖透析组(G一组)和含糖透析组(G+组),应用HPLC—MS/MSQ—TOF检测G-组和G+组血液透析前、血液透析后血清样本d用主成分分析法(PCA)、正交信号校正一偏最小二乘判别分析法(OSC.PLS—DA)分析数据,鉴别代谢物的差异。结果:(1)血液透析前及血液透析后PCA模型均无法区分G-组和G+组样本。OSC—PLS.DA模型能有效区分血液透析后G-组和G+组样本。(2)对OSC—PLS—DA模型中变量投影重要性(VIP)〉3的变量进行配对样本t检验,P〈0.05的物质为主要差异代谢物,鉴定出G+组升血糖、增加糖异生水平的物质氢化可的松和石胆酸含量较G-组低,可以参与糖异生、也是一种兴奋性神经递质的物质天冬氨酸含量亦较低,而反映氧化应激水平的指标Ⅳ-甲基烟酰胺和二羟基前列腺素F水平较G-组高。结论:通过代谢组学方法证实,单次使用含糖透析液较无糖透析液DN维持性血透患者内代谢状态稳定,减少糖异生,可能在改善患者营养状态具有优势,同时可能对脑细胞有潜在保护作用,但从目前实验结果来看可能有加重患者氧化应激状态的风险。
AIM: To investigate the metabolic features of maintenance hemodialysis patients with diabetic ne- phropathy treated with glucose-added dialysate (containing glucose at concentration of 5.5 mmol/L for one time) by high- performance liquid chromatography/quadrupole time-of-flight mass spectrometry (HPLC-MS/MS Q-TOF). METHODS: Self-control study was conducted in 10 maintenance hemodialysis patients with diabetic nephropathy, who were dialyzed with glucose-free dialysate for one time (as glucose-free dialysate group, G- group) and then changed to glucose-added di- alysate for another time (as glucose-added dialysate group, G + group). The serum samples from the patients in G- group and G ~ group before and after hemodialysis were analyzed and tested by the method of HPLC-MS/MS Q-TOF. In order to identify the differential metabolites, the metabonomic data was processed by principal component analysis (PCA) and or- thogonal signal correction-partial least square discriminate analysis (OSC-PLS-DA). RESULTS : Regardless of before or after hemodialysis, the PCA model could not distinguish the serum samples from G ~ group and G- group, but the samples could be effectively distinguish by OSC-PLS-DA model. The substances lined with variable importance in projection (VIP) value 〉 3 in the OSC-PLS-DA model and P 〈 0.05 in the paired sample t-test as differential metabolites of the 2 groups and included metabolites such as hydrocortisone, lithocholic acid, aspartic acid, N-methyl niacinamide and dihydroxypros-taglandin F. The concentrations of hydrocortisone and lithochlic acid, which was able to raise the levels of blood glucose and gluconeogenesis, were lower in G ~ group than those in G- group. The concentration of aspartic acid, which was in- volved in gluconeogenesis and also a kind of excitatory neurotransmitter, was lower in G ~ group than that in G- group. The concentrations of N-methyl niacinamide and dihydroxyprostaglandin F, which reflected the level of oxidative stress, were h