脉压差增大患者的血清代谢组特征研究

The characteristics of serum metabolome of patients with high pulse pressure

目的总结脉压差增大患者的血清代谢组特征。方法本研究选取2014年9月至2015年11月自开滦医院(课题合作单位)纳入的脉压差增大受试者21例(脉压差≥60 mmHg),脉压差正常者103例(脉压差<60 mmHg)。通过队列人群血清样本进行的液相色谱-质谱检测,分析研究组和对照组人群的血清中代谢物的组成,揭示血液循环中的代谢物在脉压差高患者中的改变情况。结果临床指标显示,与脉压差正常的对照组人群比较,脉压差高组受试者血糖水平较高[6.01(5.58,6.78)mmHg比5.36(4.98,5.84)mmHg,P<0.0001],肾功能受损[73.00(66.00,98.11)μmol/L比70.00(60.00,78.25)μmol/L,P=0.019];血脂,包括低密度脂蛋白[2.93(2.64,3.25)mmol/L比2.41(2.03,2.86)mmol/L,P=0.004]和高密度脂蛋白[1.40(1.24,1.71)mmol/L比1.23(1.06,1.35)mmol/L,P=0.001]紊乱明显。在正离子和负离子模式下的代谢组数据表明,脉压差高组与对照组人群的血清代谢组特征经PLS-DA和OPLS-DA聚类分析可显著区分。PLS-DA在负离子模式下,第一主成分的可解释度间差异为0.047;正离子模式下,第一主成分的可解释度间差异为0.0345。在脉压差高组中,乙酸、丙酮醛、2-酮丁酸等显著富集;丙酮酸、L-乳酸、马来酸等明显减少。此外,观察到差异代谢物之间呈现较为复杂的协同或互斥关系,如乙酸与D-葡萄糖、丙酮醛、2-羟基己二酸等呈正相关;L-谷氨酸与D-葡萄糖、丙酮醛、2-羟基己二酸等呈负相关。血脂、血糖、尿酸、血红蛋白、性别等临床代谢性指标与戊二酸、衣糠酸、棕榈酸、丙酮酸以及D-葡萄糖、月桂酸等差异代谢物呈显著相关。结论脉压差增大患者的血清代谢组的结构和组成呈现病理性改变,患者肠道微生物的改变可能参与脉压差增大的病理生理过程。

Objective To explore the composition of serum metabolome in patients with high pulse pressure.Methods 21 patients with high pulse pressure(≥60 mmHg)were included as the study group,and 103 individuals with normal pulse pressure(<60 mmHg)were enrolled into the control group.Liquid chromatogram mass spectrometry(LC-MS)was used to measure and compare the composition of metabolites in the serum of the patients.Results Compared with the control group,the blood glucose level was higher in the high pulse pressure group[6.01(5.58,6.78)mmHg vs.5.36(4.98,5.84)mmHg,P<0.0001];and the renal function was impaired[73.00(66.00,98.11)μmol/L vs.70.00(60.00,78.25)μmol/L,P=0.019];serum lipids,including low density lipoprotein[2.93(2.64,3.25)mmol/L vs.2.41(2.03,2.86)mmol/L,P=0.004]and high density lipoprotein[1.40(1.24,1.71)mmol/L vs.1.23(1.06,1.35)mmol/L,P=0.001]were significantly disordered.In both positive and negative ion modes,the serum metabolome characteristics between the 2 groups were significantly distinguished by PLS-DA and OPLS-DA clustering analysis.For PLS-DA in the negative ion mode,the first principal component accounted for 0.047 of the variances among the interpretable degrees.In the positive ion mode,0.0345 of the difference between the interpretable degrees of the first principal component was observed.In addition,complex synergistic or mutually exclusive relationships were observed among differential metabolites.For example,acetic acid was positively correlated with D-glucose,acetone aldehyde and 2-hydroxyadipic acid.L glutamic acid was negatively correlated with D-glucose,acetone aldehyde and 2-hydroxyadipic acid.Serum lipid,blood glucose,uric acid,hemoglobin,gender and other clinical metabolic indicators were significantly correlated with glutaric acid,chfurfuric acid,palmitic acid,pyruvate,D-glucose,lauric acid and other differential metabolites.Conclusions The structural characteristics and composition of serum metabolome in patients with high pulse pressure difference present pathological changes,and changes in intestinal microorganisms in patients may participate in the pathophysiological process of increased pulse pressure difference.