慢性阻塞性肺疾病稳定期肺气虚证及其中药干预的血浆代谢组学研究

Plasma Metabonomics Studies on the Stable Phase Chronic Obstructive Pulmonary Disease Patients of Fei-qi Deficiency Syndrome and the Chinese Materia Medica Intervention

目的运用代谢组学方法研究慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)稳定期肺气虚证及其中药干预的血浆代谢组学特征,探索其可能存在的生物标记物。方法选择40例COPD稳定期肺气虚证患者(肺气虚证组),给予六味补气胶囊进行干预,并设健康对照组(37名)。分别对健康对照组及肺气虚证组药物干预前后进行肺功能检查;采用高效液相色谱-二极质谱联用仪检测血浆代谢物,利用主成分分析(principal component analysis,PCA)和偏最小二乘法(partial least squares,PLS)对数据进行统计分析,比较两组血浆代谢组学原始谱图和数据。进行两组全谱氨基酸代谢组学检测。结果与健康对照组比较,肺气虚证组治疗前肺功能明显下降(P<0.05),治疗30天后仍低于健康对照组(P<0.05)。肺气虚证组治疗前的代谢谱与健康对照组明显不同,但治疗后有向健康对照组回归的趋势。发现15种COPD肺气虚证可能的疾病标记物。两组氨基酸代谢各有特点。结论运用血浆代谢组学方法可以发现COPD稳定期肺气虚证患者存在代谢谱和氨基酸代谢改变,并发现其潜在的疾病标记物。对COPD稳定期肺气虚证患者进行中医药干预,其代谢谱和氨基酸代谢具有积极的变化。

Objective By using the metabonomics method,to study the plasma metabonomics of the stable phase chronic obstructive pulmonary disease（COPD） patients of Fei-qi deficiency syndrome（FQDS）,and of Chinese materia medica（CMM） intervention,thus exploring possibly existent biomarkers.Methods Forty stable phase COPD patients of FQDS were recruited as Group A.Liuwei Buqi Capsule（LWBQC） was given to them as intervention.A healthy control group（Group B,37 cases） was set up.The pulmonary function test was performed on patients in Group B and Group A before and after intervention.The plasma metabolites were detected using high performance liquid chromatography-mass spectrometry（HPLC-MS/MS）.Statistical data were analyzed using principal component analysis（PCA） and partial least squares（PLS）.The original spectrum and data of plasma metabonomics were compared between the two groups.The whole spectrum amino acid metabonomics tests were performed in the two groups.Results Compared with Group B,the pulmonary function significantly decreased before intervention in Group A（P0.05）.The pulmonary function was more mildly improved after 30 days′ treatment than before treatment,but still lower than it in Group B（P0.05）.The metabolic spectrum before treatment in Group A was significantly different from Group B,but showing regressive trend to Group B after treatment.Fifteen possible disease markers were found in COPD patients of FQDS.Results of the whole spectrum of amino acid metabolomics showed different features.Conclusions The changes of metabolic spectrum and amino acids could be found in the stable phase COPD patients of FQDS using plasma metabonomics,and potential markers could be detected.The intervention of the stable phase COPD patients of FQDS by Chinese medicine could brought positive changes in the metabolic profiling and amino acid metabolism.