Metabolomic study on bleomycin-induced pulmonary fibrosis rat models at different stages / 中国药理学通报

ABSTRACT

Aim To study the variations of endogenous differential metabolites and metabolic pathways in PF rat model induced by bleomycin based on GC-MS.Methods The rat model for pulmonary fibrosis was induced by intratracheal instillation of bleomycin.Model rats were randomly divided into 7 days group of PF model(M7), 14 days group of model(M14), 21 days group of model(M21)and 28 days group of model(M28), with 6-8 rats in each group.On the 8th, 15th, 22nd and 29th days of the modeling, the rat model was evaluated by histopathology and hydroxyproline(HYP)detection.The non-targeted metabolomics was studied by GC-MS in order to find the related metabolites in the serum of PF rats and the metabolic pathways were analysed by MetaboAnalyst.Results Compared with control group, the phenomenon of rat lung lesions gradually appeared in each model group(M7, M14, M21, M28)with the modeling process.9, 14, 35, and 13 statistically significant metabolites were screened and identified respectively in M7, M14, M21 and M28.Among them, glycerol and phosphate were the early significant changes of pulmonary fibrosis.3-(3-hydroxyphenyl)propionic acid, alanine, galactonic acid, and serine changed significantly in the later stages of pulmonary fibrosis, and linoleic acid was the common main different metabolite.The main pathways affecting metabolism involved lipid metabolism, amino acid metabolism.Conclusion Abnormal amino acid metabolism and lipid metabolism are the main metabolic characteristics during the formation and development of PF by BLM.