Metabolomics study on the mechanism of ulcerous wound healing improved by cerium oxide nanocubes in diabetic rat

Abstract

Objective To investigate the metabolic changes induced by cerium oxide (CeO2) nanoparticles in ulcerous wound tissues of diabetic GK rats using non-target metabolomics. Methods Twenty male GK rats with 8-10-week age and (256±3) g weight were randomly divided into normal saline group (10 rats) and CeO2 nanoparticles group (10 rats). Two skin lesions with a diameter of 8 mm deep to the muscle layer were created symmetrically on both sides of the spine of the dorsal scapulae of the rats. The wounds were administered with saline or CeO2 nanoparticles daily for 7 days, and the rats were sacrificed on day 7 for HE staining and metabolomics analysis. Liquid chromatography-mass spectrometry was used to detect the changes of metabolites in rat wound tissues, and differential metabolites were screened by principal component analysis and orthogonal partial least squares discriminant analysis. Results Compared with the normal saline group, the HE staining in the rats of CeO2 nanoparticles group had fewer inflammatory cells and more regular fibroblasts. A total of 15 different metabolites and 6 metabolic pathways that were significantly interfered with the experimental conditions were screened, including purine metabolism, glycine, serine and threonine metabolism, arachidonic acid metabolism, biosynthesis of unsaturated fatty acids, pantothenate and CoA biosynthesis and citrate cycle. Conclusions Nano-cerium oxide can significantly improve the wound healing by regulating glucose, lipid and amino acid metabolism of the metabolic network in GK rat wounds, and up-regulating the signaling pathways of anti-inflammatory and anti-oxidative stress. Key words: Diabetes mellitus; Wound healing; Cerium oxide nanocubes; Metabolomics; High resolution mass spectrometry