基于LC-MS的小儿哮喘发作期痰热阻肺与非痰热阻肺证代谢标记物研究

Biomarkers Research on Different Syndromes of Children with Exacerbated Asthma:A LC-MS-based Metabolomics Analysis

目的:分析小儿支气管哮喘发作期痰热阻肺证与非痰热阻肺证尿液代谢谱,探索中医不同证候生物学标记物差异。方法:收集24例痰热阻肺证、20例非痰热阻肺证患儿尿液进行液相色谱-质谱检测,运用XCMS Online和Metabo Analyst分析平台确定差异性代谢物及代谢通路。结果:痰热阻肺证与非痰热阻肺证间能够良好区分,一系列有机酸、氨基酸、脂、酮类等差异性代谢物及代谢通路被确定。与痰热阻肺证相比,非痰热阻肺证组患儿尿中蛋氨酸、琥珀酸、赖氨酸、肌酸、犬尿氨酸、环腺苷酸等多种有机酸、氨基酸,以及多种脂类、酮类化合物含量升高,仅有羟基吲哚乙醛含量降低,主要涉及生物素代谢、色氨酸代谢等5条代谢通路异常。结论:小儿支气管哮喘不同证型间存在代谢标记物与代谢通路基础,可能是中医不同证候区别的本质。

Objective： By analyzing urinary metabolic profiles of heat-phlegm obstructing lung syndrome and non-heat-phlegm obstructing lung syndrome in children with exacerbated asthma to explore potential metabolic biomarkers between different syndromes.Methods： Twenty-four sick children with Heat-phlegm obstructing lung syndrome and twenty sick children with non-heat-phlegm obstructing lung syndrome were enrolled. Urine samples were collected,and urine metabolites profiles were analyzed by LC-MS coupled with a suite of statistical analyses. Results： Clear separations between heat-phlegm obstructing lung syndrome and non-heatphlegm obstructing lung syndrome existed. Differential metabolites and several metabolic pathways related organic acids,amino acids,fat,ketone compound were identified. Compared with heat-phlegm obstructing lung syndrome group,the levels of organic acids,amino acids,fat,ketone compound were upregulated,such as methionine,succinic acid,lysine,creatine,kynurenine,and cyclic AMP,and only hydroxy indole acetaldehyde were down in urine with non-heat-phlegm obstructing lung syndrome. Furthermore,five abnormal metabolic pathways,such as biotin metabolism,tryptophan metabolism were identified. Conclusion： The basis of metabolic biomarkers and pathways in children with bronchial asthma exists in different syndrome types,which may be the essence of different TCM syndromes.