| Objective:Through the successful establishment of a rat middle cerebral artery local embolism(MCAO)model to simulate the process of ischemic stroke in the human body,based on liquid chromatography-mass spectrometry metabolomics technology,dynamic monitoring of the metabolic profile of serum samples,observe the metabolic disorders caused by ischemic stroke,screen the differentially expressed metabolites after the intervention of Panax notoginseng,and explore the metabolic mechanism of Panax notoginseng to exert brain protection,provide experimental basis for the clinical application of Panax notoginseng.Methods:(1)In study,21 rats of SPF grade were randomly divide into three groups:sham operation group,model group and intervention group,with 7 rats in each group.Model group and intervention group were used to establish MCAO rat model by thread embolization method.Rats in sham operation group only had blood vessels isolated without thread embolization.The sham operation group and the model group were given distilled water gavage,and the intervention group was gavage with Panax notoginseng,twice a day for 7consecutive days.Dynamically record the scores of each group of rats according to the neuroscore scoring standard to evaluate the success of the MCAO model and the anti-ischemic effect of Panax notoginseng;(2)Collect serum samples from each group of rats,use LC-MS metabolomics technology to detect the changes of endogenous metabolites in the serum of each group of rats,and use multivariate statistical analysis methods to perform pattern recognition analysis on the data,and compare the differences in metabolic profiles between groups;(3)Compared with the sham operation group,observe the changes of endogenous metabolites in the serum of rats in the model group,and analyze the metabolic disorders caused by ischemic stroke;(4)Compared with the model group,analyze the metabolic changes in the serum samples of rats in the intervention group under the action of Panax notoginseng;(5)Based on the KEGG database,using the variable importance projection(VIP)value combined with the T test to screen the differentially expressed metabolites under the intervention of Panax notoginseng and further conduct metabolic pathway enrichment analysis,study the effect of Panax notoginseng on metabolic disorders and specific metabolic pathways in ischemic stroke.Results:(1)After the treatment of Panax notoginseng,the neurological function of th e rats in the intervention group recovered to varying degrees,suggesting that Panax notoginseng can effectively improve the symptoms of neurological deficits and has a protective effect on the brain;(2)Based on the LC-MS metabolomics platform,the metabolite profile analysis was performed according to PCA,(O)PLS-DA and other pattern recognition analysis methods.the results showed that the quality of the model was good,and the metabolic profile between each group was well distinguished;(3)A total of 23 metabolites with significant differences were screened between the sham operation g-ro up and the model group.Among them,the content of 15 different endogenous metabolit-es including creatine,glutamic acid,alanine,γ-aminobutyric acid,and phosphatidylethan-ola mine increased significantly,while the content of 8 different endogenous metabolites,including phosphatidylcholine,ethyl arachidonic acid,docosahexaenoic acid,docosapentaenoic acid,and N-acetyl-L-aspartic acid,was significantly reduced,involved in purine metabolism;glutamate,alanine and aspartic acid metabolism;glycine;serine and threonine metabolism;niacin and nicotinamide metabolism pathways;(4)After the intervention of Panax notoginseng,15 metabolites with significant differences were significantly adjusted(P<0.05),including 6 up-regulated endogenous metabolites such as arachidonic acid,glycerophospholipid choline,docosahexaenoic acid,and phosphatidylcholine,and 9 downregulated endogenous metabolites such as glutamic acid,aspartic acid,γ-aminobutyric acid,phosphatidylethanolamine,carnosine,etc,participate in glycerophospholipid metabolism in the body;metabolism of pantothenic acid and coenzyme Co A;metabolism of alanine,aspartic acid,and glutamate;metabolism of β-alanine;degradation and biosynthesis of valine,leucine,and isoleucine;Niacin and Niacinamide metabolic pathways.Conclusion:(1)Panax notoginseng can effectively improve the symptoms of neurological deficits and has a protective effect on the brain;(2)Panax notoginseng can improve the metabolic disorder caused by ischemic stroke.It may play a role in correcting amino acid metabolism,energy metabolism,glycerophospholipid metabolism,fatty acid metabolism and other ways. |
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