基于转录组学联合代谢组学探究异鼠李素防治肝纤维化的作用机制OA

Objective To elucidate the molecular mechanism of isorhamnetin in preventing and treating hepatic fibrosis through multi-omics integrated analysis,and to provide a scientific basis for its development and application.Methods KM mice were divided into a blank group,a hepatic fibrosis model group,and an isorhamnetin treatment group.Alterations in liver histology and function were assessed by hematoxylin-eosin(HE)staining,Masson's trichrome staining,Sirius red staining,and liver function tests.Transcrip-tomics and metabolomics were employed to detect differentially expressed genes and differential metabolites,respectively.Correlation analysis was performed between the differentially expressed genes(DEGs)and differentially abundant metabolites(DAMs).Molecular biology techniques were used to determine the expression of the differential molecules.Results HE,Masson's trichrome,and Sirius red staining,along with liver function tests,revealed that isorhamnetin significantly improved liver histopathological changes.Transcrip-tomic analysis identified 255 DEGs between the isorhamnetin and model groups.These DEGs were primarily enriched in signaling path-ways such as linoleic acid metabolism,arachidonic acid metabolism,glutathione metabolism,and unsaturated fatty acid biosynthesis.Metabolomic analysis revealed 451 DAMs between the isorhamnetin and model groups.These DAMs were enriched in multiple path-ways,mainly involving unsaturated fatty acid biosynthesis,ferroptosis,arachidonic acid metabolism,and autophagy.Following differ-ential analysis between the isorhamnetin and model groups,correlation analysis of the obtained DEGs and metabolites showed good model correlation,and they were primarily located in pathways such as unsaturated fatty acid biosynthesis.Molecular biology experi-ments confirmed that isorhamnetin promoted the expression of stearoyl-CoA desaturase 1(SCD1)and elongation of very long chain fatty acids protein 3(ELOVL3),and the difference was statistically significant compared to the model group.Conclusion Isorhamnetin may prevent and treat hepatic fibrosis by targeting SCD1 and ELOVL3 molecules and influencing unsaturated fatty acid metabolism.