Objective To investigate the role of cerebrovascular smooth muscle cells(CVSMCs)in hypobaric hypoxic brain injury in mice and its possible mechanism.Methods Male C57BL/6J mice were randomly divided into plain group(Sham group)and plateau group(HA group),with 10 mice in each group.HE staining,immunohistochemistry,immunofluorescence and Western blotting were used to observe brain injury and functional changes of cerebrovascular smooth muscle(CVSM)in each group.Primary CVSMCs of another 20 C57BL/6J mice were isolated and cultured,and a cellular hypoxia model was established.Transcriptome sequencing of hypoxic(Hypoxia group)and normoxic(Control group)cells was performed by RNA-seq technology.Differentially expressed genes(DEGs)were screened for GO enrichment analysis and KEGG pathway enrichment analysis,and qRT-PCR was used to verify the accuracy of sequencing results.Results The simulated high-altitude environment caused neuron damage in mice,and this damage was accompanied by changes in the contractile function of CVSM.RNA-seq results showed that there were 511 DEGs(fold change>2 and P<0.05)in the Hypoxia group compared with the Control group,including 298 up-regulated DEGs and 213 down-regulated DEGs.In GO enrichment analysis,DEGs were mainly enriched in the structure and function of mitochondria and the related pathways of glycometabolism.In KEGG pathway enrichment analysis,glycolysis/gluconeogenesis,biosynthesis of amino acids and RIG-I-like receptor signaling pathways were significantly enriched(P<0.05).Conclusion CVSMCs can play a role in hypobaric hypoxic brain injury by changing energy metabolism,substance metabolism,signal transduction and other ways.This study provides a new direction and idea for further study on the mechanism of CVSMCs in hypobaric hypoxic brain injury.