溃疡性结肠炎活动期大肠湿热证患者血清代谢组学特征分析

Analysis of serum metabolomic characteristics of patients in the active stage of ulcerative colitis with syndrome of dampness-heat in large intestine

目的 通过非靶代谢组学技术获取溃疡性结肠炎(UC)活动期大肠湿热证患者代谢组学特征,为推动病证结合、微宏观结合的中医药辨证理论体系提供依据。方法 采用非靶代谢组学技术检测159例UC活动期患者(大肠湿热证81例、非大肠湿热证78例)和30名健康志愿者的血清。构建正交偏样本最小二乘法判别分析模型,筛选组间变化明显的代谢产物,以代谢物第一主成分的变量重要性投影≥1、P<0.05且差异倍数(FC)>1.20或FC<0.83为标准筛选差异代谢物。选用京都基因和基因组数据库(KEGG)对差异代谢物进行注释,MetaboAnalyst软件进行通路分析。结果 UC活动期大肠湿热证与非大肠湿热证患者比较,在正离子模式下共筛选出99种差异代谢物,其中,48种代谢物上调,51种代谢物下调;负离子模式下共筛选出38种差异代谢物,其中,19种代谢物上调,19种代谢物下调。KEGG富集分析共富集到21条代谢通路,通路分析显示主要涉及色氨酸代谢、鞘脂代谢、甘油磷脂代谢和嘧啶代谢4条代谢通路。结论 UC活动期大肠湿热证患者存在代谢通路异常,可为中医药辨证治疗UC大肠湿热证提供依据。

Objective To obtain the metabolomics characteristics of patients in the active stage of ulcerative colitis(UC)with syndrome of dampness-heat in large intestine through non-target metabolomics technology,and to provide a basis for promoting the theoretical system of traditional Chinese medicine(TCM)syndrome differentiation of disease syndrome combination and micro-macro combinations.Methods Non-target metabolomics technology was used to detect the serum samples from 159 patients in the active stage of UC(81 cases with syndrome of dampness-heat in large intestine and 78 cases with syndrome of non-dampness-heat in large intestine)and 30 healthy volunteers.The orthogonal partial sample least squares discriminant analysis model was constructed to screen metabolites with significant changes among groups.The variable importance in projection≥1,P<0.05,and fold change(FC)>1.20 or FC<0.83 were used as the criteria for the screening of differential metabolites.The Kyoto Encyclopedia of Genes and Genomes(KEGG)was used to annotate differential metabolites,and MetaboAnalyst software was used for pathway analysis.Results Between patients in active stage of UC with syndrome of dampness-heat in large intestine and syndrome of non-dampness-heat in large intestine,a total of 99 differential metabolites were screened in the positive ion mode,of which 48 were upregulated and 51 were downregulated.In the negative ion mode,a total of 38 differential metabolites were screened,of which 19 were upregulated and 19 were downregulated.The KEGG enrichment analysis showed that there were 21 metabolic pathways,and the pathway analysis showed that there were mainly four metabolic pathways involved in tryptophan metabolism,sphingolipid metabolism,glycerophospholipid metabolism,and pyrimidine metabolism.Conclusion Patients in the active stage of UC with syndrome of dampnessheat in large intestine have abnormal metabolic pathways,which can provide a basis for TCM syndrome differentiation and treatment for UC with syndrome of dampness-heat in large intestine.