Objective To investigate the protective effect of cyclic peptide GYHHQYTG(cGY-8)on acute hypoxic brain injury in mice and its possible mechanism.Methods BALB/c mice were randomly divided into control group and cGY-8 administration group with different doses to observe the survival time of mice in each group under atmospheric pressure and hypoxia and select the optimal drug concentration.Subsequently,BALB/c mice were randomly divided into normal oxygen group(Nor group),model group(M group),acetazolamide group(ACZ group),and low-dose,medium-dose,and high-dose cGY-8 administration groups,with 6 mice in each group.The brain injury of the mice in each group was observed after hypobaric hypoxia treatment.Fifteen BALB/c mice were randomly divided into normal oxygen group(Nor group),hypoxic group(Hy group),and hypoxic administration group(cGY-8 group).After normal pressure closed hypoxia treatment,RNA was extracted from whole brain tissue for transcripome sequencing,and differentially expressed genes(DEGs)were screened for GO enrichment analysis and KEGG pathway enrichment analysis.The accuracy of the sequencing data was verified by qRT-PCR.Results cGY-8 prolonged the survival time of mice under normal pressure and hypoxia,and reduced the water content and oxidative stress response of mice under low pressure and hypoxia.Transcriptomic analysis showed that there were 678 DEGs in the Hy group compared with the Nor group(the change was more than 2 times;P＜0.05),and the cGY-8 treatment could bring back 91 DEGs.GO enrichment analysis showed that 91 DEGs were mainly enriched in signal transduction,inflammatory response,redox enzyme activity,etc.KEGG enrichment analysis showed that 91 DEGs were mainly enriched in cGMP-PKG signal pathway and calcium ion signal pathway.Conclusion cGY-8 may protect mice from hypoxic brain injury by regulating energy metabolism and alleviating Ca2+overload in brain cells.This study provides a new idea for the development of drugs for the prevention and treatment of high-altitude cerebral edema.
维普
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