摘要Microglia-mediated neuroinflammation plays a crucial role in ischemic stroke;consequently,understanding its regulation could facilitate the development of therapies for ischemic stroke.Chemerin 15,a 15-amino acid peptide derived from chemerin,exerts powerful anti-inflammatory effects through ChemR23,modulates macrophage polarization,and diminishes inflammatory cytokine expression in peripheral inflammation models.However,its effects on microglia and stroke remain unclear.In this study,we used an in vitro oxygen/glucose deprivation BV2 cell model and a mouse model of ischemia-reperfusion injury to investigate the role of chemerin 15 in stroke and the underlying mechanisms.We co-cultured BV2 microglial cells with HT-22 hippocampal neurons and observed that chemerin 15 reduced apoptosis in HT-22 cells.Furthermore,we found that chemerin 15 binds to the ChemR23 receptor on the cell surface,inducing its internalization.This process regulated the activity of adenosine 5'-monophosphate-activated protein kinase and inhibited its downstream target nuclear factor kappa B.These effects could be reversed by treatment with α-NETA,a ChemR23 inhibitor.In mice with ischemia-reperfusion injury,chemerin 15 modulated microglial polarization,reduced infarct volume and neuronal apoptosis,and facilitated cognitive and neurological function recovery.Our findings suggest that chemerin 15 suppresses the microglia-mediated inflammatory response,decreases neuronal apoptosis,and enhances long-term neurological function recovery by inducing ChemR23 internalization and regulating the adenosine 5'-monophosphate-activated protein kinase/nuclear factor kappa B signaling pathway.