慢性阻塞性肺病稳定期模型大鼠支气管肺泡灌洗液的代谢组学研究

Metabonomic study of alveolar lavage fluid in rats with stable chronic obstructive pulmonary disease

目的:基于代谢组学方法研究慢性阻塞性肺病(chronic obstructive pulmonary disease, COPD)稳定期大鼠支气管肺泡灌洗液(bronchoalveolar lavage fluid, BALF)的潜在生物标志物。方法:采用烟熏联合细菌反复感染的方法制备COPD稳定期模型大鼠。采用超高效液相色谱-串联质谱技术采集大鼠的BALF数据,利用多元统计分析软件筛选差异代谢物,再结合数据库鉴定潜在生物标志物,并进行代谢通路分析。结果:多元统计分析结果显示,正常组与模型组BALF代谢物发生显著变化。通过比对数据库,共鉴定出30个差异性代谢物,主要涉及到体内的氨酰基-tRNA的生物合成,甘氨酸、丝氨酸和苏氨酸的代谢,鞘脂代谢,苯丙氨酸代谢和花生四烯酸代谢等8条代谢通路。结论:基于代谢组学研究COPD稳定期的BALF代谢物变化,寻找COPD稳定期相关代谢标志物,为治疗COPD提供理论参考。

OBJECTIVE To explore the potential biomarkers of bronchoalveolar lavage fluid(BALF) in rats with stable chronic obstructive pulmonary disease(COPD) based upon metabonomics.METHODS A rat stable COPD model was established by recurrent bacterial infections plus smoking. Ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) was employed for collecting the data of lavage fluid. Multivariate statistical analytic software was utilized for metabolite screening. And the database was accessed for identifying potential biomarkers and metabolic pathways.RESULTS Multivariate statistics revealed a significant change of BALF metabolite between control and model groups. Through a database comparison, a total of 30 different metabolites were correlated with the in vivo biosynthesis of aminoacyl-tRNA and the metabolisms of glycine, serine, threonine, sphingolipid, phenylalanine, arachidonic acid and enoic acid.CONCLUSION Based upon the studies of metabolite changes in BALF of stable COPD metabolomics, stable COPD-related metabolic markers provide theoretical references for the treatment of lung diseases.