肺气虚型慢性阻塞性肺疾病大鼠模型及其中药干预的血浆代谢组学研究

Plasma metabonomics studies and Chinese materia medica intervention on the chronic obstructive pulmonary disease rat model with lung-qi deficiency syndrome

目的:运用代谢组学方法研究肺气虚型COPD大鼠模型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:将56只大鼠随机分为对照组和模型组。造模成功后,从模型组中随机分出8只大鼠,设立干预组,进行中药干预。对各组进行肺功能检测、比较;采用高效液相色谱-二极质谱联用仪(HPLC-MS/MS)检测血浆代谢物,利用主成分分析和偏最小二乘法对数据进行统计分析,比较3组血浆代谢组学原始谱图和数据。结果:与对照组比较,模型组肺功能明显下降(P<0.05),干预组肺功能较模型组有显著改善(P<0.05)。模型组的代谢谱与对照组明显不同,干预组有向对照组回归的趋势。发现10种COPD肺气虚证可能的疾病标记物。结论:本研究建立肺气虚型COPD大鼠模型的代谢组学研究方法及其代谢图谱,发现其可能的疾病标记物,对其进行中药干预有积极的变化。为中医药诊疗COPD的研究提供了新的方法。

Objective： By using the metabonomics method, to study the plasma metabonomics and the Chinese materia medica（CMM） intervention of the stable phase of chronic obstructive pulmonary disease rat model with Fei-qi deficiency syndrome（FQDS）, thus exploring possibly existent biomarkers. Methods： 56 rats were randomized into control group and model group. After the successful establishment of the models, 8 rats were randomized selected from the model group which establish the intervention group and then treated by Chinese medicine. Pulmonary function tests and comparison were conducted in all the groups. The plasma metabolites were detected by 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 three groups. Results： Compared with the control group, the lung function of model group was significantly decreased（P〈0.05）, compared with the model group, the pulmonary function of the intervention group had mild improved. The metabolic profiling of model group differed remarkably from that of control group; the intervention group had a regression trend to the healthy control group. Ten possible disease markers were found in COPD rats of FQDS. Conclusion： The metabonomics research method and metabolic spectrum of COPD rat model with FQDS were established, which would find the possible disease markers. The intervention of stable phase COPD rat model by Chinese medicine could bring positive changes and provide new research method for the treatment of COPD by Chinese medicine.