段飞,李曼曼,李伟霞,唐进法,王至婉
DUAN Fei,LI Man-man,LI Wei-xia,TANG Jin-fa,WANG Zhi-wan

• 1:河南中医药大学第一附属医院

摘要(Abstract)：

该研究运用非靶向代谢组学分析慢性阻塞性肺疾病(COPD)肺气虚证的潜在生物标志物，探究该证型的生物学基础。收集96例COPD肺气虚证患者(COPD肺气虚证组)及106名健康人(健康组)的血液样品，采用超高效液相色谱-四极杆-飞行时间串联质谱(UPLC-Q-TOF-MS)对2组样品的代谢轮廓进行分析，利用Progenesis QI和Simca-P软件进行多元统计分析及差异代谢物的筛查，通过MetaboAnalyst数据库构建代谢通路。最终分析鉴定得到L-胱硫醚、原卟啉原Ⅸ、西酞普兰醛等7个潜在的生物标志物。与健康组相比，西酞普兰醛、11β,17β-二羟基-4-雄烯-3-酮、N1-甲基-2-吡啶酮-5-羟基胺的含量显著上调，L-胱硫醚、原卟啉原Ⅸ、双氢睾酮、D-尿素胆原的含量则明显下降。这7个潜在的生物标志物涉及半胱氨酸和蛋氨酸代谢，卟啉和叶绿素代谢，细胞色素P450对药物的代谢，类固醇激素的生物合成，甘氨酸、丝氨酸和苏氨酸代谢以及烟酸和烟酰胺代谢共6条代谢通路，从分子生物学水平为慢性阻塞性肺疾病肺气虚证的中医证候研究提供了一定的科学依据。
The present study analyzed the potential biomarkers of chronic obstructive pulmonary disease(COPD) with lung-Qi deficiency syndrome by non-targeted metabolomics and explored the biological basis of this syndrome. Blood samples of 96 COPD patients with lung-Qi deficiency syndrome(COPD with lung-Qi deficiency syndrome group) and 106 healthy people(healthy control group) were collected, and the metabolic profiles of both groups were analyzed by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS). Multivariate statistical analysis and differential metabolite screening were carried out by using Progenesis QI and Simca-P. Metabolic pathways were constructed through the MetaboAnalyst. Seven potential biomarkers, such as L-cystathionine, protoporphyrinogen Ⅸ, and citalopram aldehyde, were identified. Compared with the results in the healthy control group, the content of citalopram aldehyde, N1-methyl-2-pyridone-5-carboxamide, and 11β,17β-dihydroxy-4-androsten-3-one was significantly up-regulated, while that of the other four compounds such as L-cystathionine, dihydrotestosterone, protoporphyrinogen Ⅸ, and D-urobilinogen was down-regulated. These potential biomarkers involved six metabolic pathways, including cysteine and methionine metabolism, porphyrin and chlorophyll metabolism, drug metabolism of cytochrome P450, steroid hormone biosynthesis, glycine, serine, and threonine metabolism, and nicotinate and nicotinamide meta-bolism. This study is expected to provide a certain scientific basis for the research on traditional Chinese medicine syndrome of COPD with lung-Qi deficiency syndrome from the molecular biology level.

关键词(KeyWords)： 慢性阻塞性肺疾病;肺气虚证;UPLC-Q-TOF-MS;代谢组学
chronic obstructive pulmonary disease;lung-Qi deficiency syndrome;UPLC-Q-TOF-MS;metabolomics

Abstract:

Keywords:

基金项目(Foundation): 中国博士后科学基金特别资助项目(2020T130032ZX);; 国家自然科学基金项目(81973791);; 河南省博士后科研项目(001801023);; 河南省中医管理局国家中医临床研究基地科研专项(2018JDZX056);; 国家重点研发计划项目(2017YFC1700103)

作者(Author): 段飞,李曼曼,李伟霞,唐进法,王至婉
DUAN Fei,LI Man-man,LI Wei-xia,TANG Jin-fa,WANG Zhi-wan

DOI: 10.19540/j.cnki.cjcmm.20211203.501

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