Objective To investigate the protective effect and mechanism of celastrol on ischemic brain injury by metabolomics and proteomics analyses.Methods The middle cerebral artery ischemia-reperfusion model was established in ICR mice.The mice were divided into control group and celastrol treatment group,and the brain injury tissues were collected for metabolomics analysis.In addition,BV2 mouse microglia was treated with LPS to induce brain injury models in vitro.After treatment with celastrol,cell samples were collected for metabolomics and proteomic analysis.Results Compared with the control group,22 metabolites in the model group were significantly enriched in aspartate metabolism,phenylalanine and tyrosine metabolism,purine metabolism,urea cycle and so on.Most of the abnormal metabolites were reversed after celastrol treatment.After LPS treatment,131 biomarkers were significantly changed in BV2 microglia,and these metabolites were significantly enriched in arginine and proline metabolism,malate-aspartate shuttle,and aspartic acid metabolism.Most of the abnormal metabolites were reversed after celastrol treatment,and 43 metabolites showed significant differences.A total of 7 590 proteins were identified in the proteomic analysis,of which LPS treatment induced differential expression of 393 proteins.Compared with LPS group,126 proteins were significantly expressed after celastrol treatment.Functional enrichment analysis showed that these differential proteins were associated with immune processes,inflammatory responses and their related signaling pathways.Conclusion Ischemic brain injury can lead to the changes of metabolites involved in aspartate and purine metabolism,and the signaling pathways involved in inflammation.Triptolide can regulate the changes of some metabolites and differential proteins.
万方数据
维普
