补肺益肾方对慢性阻塞性肺疾病大鼠尿液代谢谱的影响OA

Objective:This study aims to investigate the effects of Bufei Yishen Formula(补肺益肾方,BYF)on u-rinary metabolites in rats with chronic obstructive pulmonary disease(COPD)based on urine metabolomics using ultra-high-performance liquid chromatography-quadrupole-electrostatic field orbitrap mass spectrometry(UHPLC-QE-MS).Methods:24 SD rats were randomly divided into a normal control group,a model control group,a BYF 3.7 g/kg group,and an S-carboxymethyloysteine(S-CMC)0.14 g/kg group.Body weight,lung index,and lung wet/dry weight ratio were observed.Pulmonary function,gross lung appearance,histopathology,and ul-trastructure were detected.Urinary metabolic profiles were analyzed by UHPLC-QE-MS.Dif-ferential metabolites were analyzed by a multivariate statistical method,and enriched metabolic pathways were analyzed by the MetaboAnalyst database.Results:Compared with the normal control group,rats in the model control group showed increased lung index and lung we/dry weight ratio(P<0.01),and decreased lung function indexes including forced vital capacity(FVC),forced expiratory volume in 0.1 sec-ond(FEV0.1),and FEV0.1/FVC(P<0.01).Gross lung observations revealed enlargement and pallor of some lung lobes.Histopathological staining showed alveolar wall rupture,fusion,and inflammatory cell infiltration.Ultrastructure a-nalysis showed vacuoliza-tion of lamellar bodies in alveolar type II epithelial cells,mitochondrial cristae swelling,and in-tracellular appearance of lipid droplets.Compared with the model control group,rats in the BYF 3.7 g/kg group exhibi-ted partially restored body weight,reduced lung index and wet/dry weight ratio(P<0.05),improved pulmonary function(P<0.01),and alleviated macroscopic lung injury.A total of 180 potential urinary biomarkers were identified in the model control group,among which 106 metabolites showed a clear trend of regulation after BYF 3.7 g/kg intervention.These metabolites were mainly enriched in pathways including phenylalanine metabolism,vitamin B6 metabolism,glyoxy-late and dicarboxylate metabolism,arginine and proline metabolism,alanine,aspartate and glutamate metabolism,nicoti-nate and nicotinamide metabolism,tryptophan metabo-lism,citrate cycle,and arginine biosynthesis.Conclusions:BYF may alleviate COPD by im-proving endogenous metabolic disturbances and restoring normal metabolic activity.