Objective To explore the mechanism of action of Salidroside in the treatment of hypoxic-ischemic brain injury(HIBD)in neonatal mice by network pharmacology and experimental verification.Methods PubChem,pharm Map-per,Swiss Target Prediction and Similarity Ensemble Approach were used to search and predict the target of Salidroside ac-tion.DisGeNET,GeneCards and OMIM databases were used to obtain the HIBD disease-related targets,and intersection genes were identified by Venn diagram.The intersection gene was imported into the STRING platform to construct the protein interaction network.Combined with STRING database and Cytoscape software for visualization processing,the target was screened,and the core target was obtained through topological network analysis.DAVID database was used to analyze the GO function and KEGG pathway enrichment of potential targets.HIBD model of neonatal mice was established,sham operation group,hypoxia-ischemia group,placebo group and Salidroside group were set up,and TTC and HE staining were used to eval-uate brain injury of neonatal mice,respectively.The expressions of apoptosis-related proteins and PI3K/Akt signaling proteins were detected by Western blot.Y-maze test,tension test and corner test were used to verify the effect of Salidroside on impro-ving behavioral performance of mice.Results The network pharmacological analysis showed that 176 effective drug targets,2 173 effective disease targets,61 drug-disease intersection targets,and 10 core targets were obtained.KEGG pathway enrich-ment analysis showed that the mechanism of Salidroside was related to PI3K/Akt signaling pathway.Animal experiments showed that,compared with hypoxia-ischemia group,Salidroside promoted the expression of p-PI3K/PI3K and p-Akt/Akt,in-creased the expression of Bcl-2/Bax,inhibited the expression of Cleaved-caspase-3,reduced the damage of cortical and hipp-ocampal neurons,decreased the brain infarct volume and brain atrophy induced by HIBD,and improved the memory and mo-tor ability of mice(P＜0.05,P＜0.01).Conclusion Salidroside can improve neuronal apoptosis by activating PI3K/Akt signaling pathway,which can be used in the treatment of HIBD in neonatal mice.
维普
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