Berberine alleviates atorvastatin-induced intracerebral hemorrhage in zebrafish by regulating the JAK/STAT pathway
Objective To investigate the protective effect of berberine(BBR)against atorvastatin(ATV)-induced zebrafish intracerebral hemorrhage(ICH)model.Methods An ATV zebrafish ICH model was used,with concurrent administration of BBR to observe hemorrhagic conditions,assess neural damage,analyze post-bleeding inflammatory factors,and evaluate swimming locomotion.Zebrafish brain tissue was isolated for transcriptome sequencing analysis,and differential gene function analysis was conducted using the gene ontology(GO)and kyoto encyclopedia of genes and genomes(KEGG)databases to explore the mechanism of BBR effects.Results ATV(2 μmol/L)significantly induced cerebral hemorrhage and post-hemorrhagic injury in zebrafish juveniles,with severe hemorrhage observed in 80%of zebrafish at 48 hours post-administration.The number of neurons was significantly reduced after hemorrhage.Treatment with BBR resulted in a decrease in the average bleeding area from 0.019 mm2 to 0.011 mm2,along with alleviation of nerve damage and inflammation.Transcriptome sequencing revealed 48 overlapping genes among the differentially expressed genes(DEGs)in the model group vs.control group and the DEGs in the BBR treatment group vs.model group.KEGG analysis showed significant enrichment of the JAK/STAT signaling pathway.Four genes,il11b,stat1b,lepa and lepb,exhibited significant changes,which were validated through qPCR,confirming consistency with the sequencing results.Conclusion BBR protects against ATV cerebral hemorrhage and post-hemorrhagic brain damage in zebrafish,and the JAK/STAT signaling pathway may be involved in BBR effects.
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