Mechanism of Xingnaojing injection intervention in cerebral ischemiareperfusion rat model based on GC-MS metabolomics

Objective:To investigate the protective effect of Xingnaojing injection on cerebral ischemia-reperfusion in rats and its metabolic pathway and mechanism.Methods:The cerebral ischemia reperfusion model of rats was established by suture occlusion.After successful model evaluation,he rats were randomly divided into model group and Xingnaojing group with eight rats in each group.In the sham operation group,only blood vessel separation was performed without embolization.Xingnaojing group was given intraperitoneal injection,model group and sham operation group were given the same dose of normal saline,twice a day.Three days later,HE staining and GC-MS metabolomics were used to detect the changes of endogenous metabolites in the rat brain tissue.Principal component analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLS-DA)were used to screen out differential metabolites and analyze their metabolic pathways.Results:Endogenous metabolites were disturbed after cerebral ischemia-reperfusion injury in rats.Seventy-one different metabolites were screened from the model group and the sham group,of which three were down-regulated and sixty-eight were up-regulated.Eighty-eight different metabolites were found between Xingnaojing group and sham operation group,among which eight were down-regulated and eighty up-regulated.After screening of Xingnaojing group and model group,twelve different metabolites were obtained,among which seven were down-regulated and five up-regulated.By analyzing the differences of metabolites,Xingnaojing injection was considered to be involved in the metabolic pathway after cerebral ischemia-reperfusion in rats,including amino acid metabolism(beta alanine metabolism,alanine,glutamic acid and aspartic acid metabolism,histidine metabolism,arginine and proline metabolism),glutathione metabolism,pyrimidine metabolism,ABC transporter,nitrogen metabolism and other metabolic pathways.Conclusion:Xingnaojing injection can restore the levels of metabolites in cerebral ischemia-reperfusion rats in certain degrees,mainly through amino acid metabolism,ABC transporter,glutathione metabolism and other metabolic pathways to regulate cerebral ischemia-reperfusion injury in rats.