不同程度的哮喘患者血浆氨基酸代谢组学特征的比较研究
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摘要
目的探讨不同严重程度(轻度、中度、重度)哮喘患者血浆氨基酸代谢组学的特征。方法收集符合支气管哮喘诊断标准的哮喘患者(轻度哮喘组、中度哮喘组、重度哮喘组各25例)和健康对照组30例。采用超高效液相联用质谱法(ultra performance liquid chromatography-mass spectrometer,UPLC-MS)检测轻度、中度、重度哮喘组和健康对照组血浆氨基酸代谢物含量的特征。结果与健康对照组比较,轻度哮喘组中的甘氨酸、丝氨酸、缬氨酸、苏氨酸、半胱氨酸、异亮氨酸、天门冬氨酸、甲硫氨酸和苯丙氨酸含量降低,差异有统计学意义(P<0.05);与健康对照组比较,中度哮喘组中的甘氨酸、丙氨酸、脯氨酸、酪氨酸、丝氨酸、缬氨酸、苏氨酸、半胱氨酸、异亮氨酸、天门冬氨酸、甲硫氨酸和苯丙氨酸含量降低,差异有统计学意义(P<0.05);与健康对照组比较,重度哮喘组中的甘氨酸、丝氨酸、半胱氨酸、天门冬氨酸和谷氨酸含量降低,丙氨酸、缬氨酸、亮氨酸、异亮氨酸、甲硫氨酸、苯丙氨酸和酪氨酸含量升高,差异有统计学意义(P<0.05)。结论不同程度哮喘组中,代谢产物的变化趋势有一定的相似性与差异,可将代谢组学运用到寻找不同程度的哮喘疾病相关特异性代谢产物之间的共性与差异性;不同程度哮喘组中,重度哮喘代谢产物的紊乱程度最明显,表明代谢产物的变化可能是判断哮喘严重程度的依据。
Objective The purpose of this study was to compare the metabolomics of all degrees of asthmatic patients.Methods 75 bronchial asthma patients were divided to severe,moderate and mild group,each group had 25 cases,30 healthy volunteers were enrolled in the healthy control group.Their plasma amino acid metabolite content were tested by ultra performance liquid chromatography and mass spectrometer.Results The content of Gly,Ser,Val,Thr,Cys,Ilu,Asp,Met,Phe in the plasma of Mild asthma group was significantly less than the one in the healthy volunteers(P <0.05).The content of Gly,Ser,Val,Thr,Cys,Ilu,Asp,Met,Phe,Ala,Pro,Tyr in the plasma of moderate asthma group was significantly less than the one in the healthy volunteers(P <0.05).The content of Gly,Ser,Cys,Asp,Glu in the plasma of severe asthma group was significantly less than the one in the healthy volunteers(P <0.05),while the content of Ala,Val,Leu,Ilu,Met,Phe,Tyr in the plasma of severe asthma group was significantly more than the one in the healthy volunteers(P <0.05).Conclusion Our result underscore the importance of metabolic phenotypes in different degree of asthma,there are some similarities and differences in the trend of metabolites,which indicates that metabonomics can be used to find the commonness and difference between the specific metabolites related to asthma in different levels.The metabolic disorders of severe asthma is most obvious in different degree asthmatic patients.This suggests that changes in metabolites may be the basis for determining the severity of asthma.
Objective The purpose of this study was to compare the metabolomics of all degrees of asthmatic patients.Methods 75 bronchial asthma patients were divided to severe,moderate and mild group,each group had 25 cases,30 healthy volunteers were enrolled in the healthy control group.Their plasma amino acid metabolite content were tested by ultra performance liquid chromatography and mass spectrometer.Results The content of Gly,Ser,Val,Thr,Cys,Ilu,Asp,Met,Phe in the plasma of Mild asthma group was significantly less than the one in the healthy volunteers(P <0.05).The content of Gly,Ser,Val,Thr,Cys,Ilu,Asp,Met,Phe,Ala,Pro,Tyr in the plasma of moderate asthma group was significantly less than the one in the healthy volunteers(P <0.05).The content of Gly,Ser,Cys,Asp,Glu in the plasma of severe asthma group was significantly less than the one in the healthy volunteers(P <0.05),while the content of Ala,Val,Leu,Ilu,Met,Phe,Tyr in the plasma of severe asthma group was significantly more than the one in the healthy volunteers(P <0.05).Conclusion Our result underscore the importance of metabolic phenotypes in different degree of asthma,there are some similarities and differences in the trend of metabolites,which indicates that metabonomics can be used to find the commonness and difference between the specific metabolites related to asthma in different levels.The metabolic disorders of severe asthma is most obvious in different degree asthmatic patients.This suggests that changes in metabolites may be the basis for determining the severity of asthma.
引文
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[8]TO T,STANOJEVIC S,MOORES G,et al.Global astIIma preva—lence in adults:findings from the cross—sectional world health survey[J].BMC Public Health,2012,12(1):200.
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[12]BRIGHTLING C E,GREEN R H,PAVORD I D.Biomarker spredicting response to corticosteroid therapy in asthama[J].Treat Respir Med,2005(4):309-316.
[13]NICHOLSON J K,HOLMES E,ELLIOTT P.The metabolome-wide association study:a newlook at human disease risk factors[J].J Proteome Res,2008,7(9):3637-3638.
[14]SAUDE E J,CHRISTOPHER D,REGUSH S,et al.Metabolomic profiling of asthama:Diagnostic utility of urine nuclear magnetic resonance spectroscopy[J].J Allergy Clin Immunol,2010(127):757-764.
[15]甄乾娜,黄小兰,张小清,等.高效液相色谱-程序波长紫外检测法同时测定血浆中的色氨酸及其代谢物[J].色谱,2011,29(5):435-438.
[16]DARRY LJ,ADAMKO MD,BRIAN D.The Metabolomics of Asthma[J].Chest,2012(141):1295-1302.
[17]吕子凡,郭非凡.氨基酸感应与糖脂代谢调控的研究进展[J].生命科学,2013,25(2):152-157.
[2]叶宏波,金晓慧.中西医结合治疗慢性阻塞性肺疾病急性发作并Ⅱ型呼吸衰竭的疗效分析[J].中华中医药学刊,2015,33(11):2778-2780.
[3]REINKE S N.GAUART-AYALA H,GMEZ C,et al.Metabolomics analysis identifies different metabotypes of asthma severityl[J].Ear Respir J,2017(49):160-174.
[4]孟欣,汪受传,谢彤,等.基于GC-MS代谢组学的RSV肺炎小鼠尿液和粪便生物标记物研究[J].南京中医药大学学报,2017,33(2):198-206.
[5]李彦东,吴琪.代谢组学技术在临床诊断中的研究进展[J].天津医药,2015,43(8):942.
[6]李錦,姜疑,贺福处.代谢组学技术及其在临床研究中的应用[J].遗传学报,2008,30(4):389-399.
[7]郭宾,戴仁科.代谢组学及其研究策略和分析方法进展[J].中国卫生检验杂志,2017,17(3):554-556.
[8]TO T,STANOJEVIC S,MOORES G,et al.Global astIIma preva—lence in adults:findings from the cross—sectional world health survey[J].BMC Public Health,2012,12(1):200.
[9]赵维薇,许文涛,王龑,等.代谢组学研究技术及其应用[J].生物技术通报,2011,12:58-63.
[10]周文芳.血浆中氨基酸检测技术探讨[J].氨基酸和生物资源,2012,34(3):25-28.
[11]安芳,张洪飞,林丽娜,等.高血压患者血浆中游离氨基酸的柱前衍生HPLC法测定[J].分析测试学报.2009,28(1):72-75,79.
[12]BRIGHTLING C E,GREEN R H,PAVORD I D.Biomarker spredicting response to corticosteroid therapy in asthama[J].Treat Respir Med,2005(4):309-316.
[13]NICHOLSON J K,HOLMES E,ELLIOTT P.The metabolome-wide association study:a newlook at human disease risk factors[J].J Proteome Res,2008,7(9):3637-3638.
[14]SAUDE E J,CHRISTOPHER D,REGUSH S,et al.Metabolomic profiling of asthama:Diagnostic utility of urine nuclear magnetic resonance spectroscopy[J].J Allergy Clin Immunol,2010(127):757-764.
[15]甄乾娜,黄小兰,张小清,等.高效液相色谱-程序波长紫外检测法同时测定血浆中的色氨酸及其代谢物[J].色谱,2011,29(5):435-438.
[16]DARRY LJ,ADAMKO MD,BRIAN D.The Metabolomics of Asthma[J].Chest,2012(141):1295-1302.
[17]吕子凡,郭非凡.氨基酸感应与糖脂代谢调控的研究进展[J].生命科学,2013,25(2):152-157.