A Metabolomic Study Of Oxygen-glucose-deprived Macrophages

Objective:The aim of our study is to identify the differential metabolites produced by macrophages under oxygen and glucose deprivation(OGD)condition compared with normal condition and metabolic pathways enriched by them through metabolomics.Methods:The macrophages were firstly divided into the normal group defined as control group and the OGD group,and the composition of metabolites were preliminarily analyzed by ultra-high performance liquid chromatography tandem mass spectrometry technology(UPLC-MS).The principal component analysis(PCA)model of the normal group and the OGD group was finally combined with the nonparametric test to screen out the statistically significant differential metabolites and metabolic pathways enriched in the OGD group compared with the normal group.Results:(1)Among the important differential metabolites produced by macrophages under OGD condition,the increased metabolites included:2-arachidonic acid glycerol,L-aspartic,deoxyadenosine,deoxyguanosine,adenine,oleate,tetradecenoic acid,palmitoleic acid and S-adenosylmethionine.(2)The decreased metabolites included:5-HT,pyruvate,NAD+,AMP,reduced glutathione,serine and tryptophan.(3)The important metabolic pathways enriched by differential metabolites produced by macrophages under OGD condition included:cysteine and methionine metabolism,glycine,serine and threonine metabolism,purine metabolism,nicotinate and nicotinamide metabolism,glutathione metabolism,arginine and proline metabolism,AMPK signaling pathway,cAMP signaling pathway,alanine,aspartate and glutamate metabolism,fatty acid biosynthesis,neuroactive ligand-receptor interaction,longevity regulating pathway,pantothenate and CoA biosynthesis and thiamine metabolism,etc.Conclusions:(1)The differential metabolite associated with M1 polarization under OGD condition was NAD+ and 5-HT;the one associated with M2 polarization under OGD condition was oleate.(2)The metabolic pathways containing differential metabolites associated with macrophage polarization produced by macrophages under OGD condition included:nicotinate and nicotinamide metabolism,thiamine metabolism,AMPK signaling pathway,cAMP signaling pathway and fatty acid biosynthesis.