Effect of asiaticoside on the blood-brain barrier injury in ischemic stroke rats by regulating the TXNIP/NLRP3 signaling pathway
ZHANG Wen
LIU Jianghua
JIN Haitao
Abstract：Objective To investigate the effect of asiaticoside(ASI)on the blood-brain barrier injury in ischemic stroke(IS)rats by regulating the thioredoxin interacting protein(TXNIP)/NOD-like receptor protein 3(NLRP3)signaling pathway.Methods A total of 108 rats in the specific pathogen-free(SPF)level were randomly assigned into sham operation group,IS group,low-dose and high-dose ASI groups,high-dose ASI+OE-NC group,and high-dose ASI+OE-TXNIP(TXNIP activator)group,with 18 rats in each group.Except for rats in the sham operation group,IS rat model was created in the remaining groups using the middle cerebral artery occlusion method.After successful modeling,drugs were immediately administered for a total of 2 consecutive weeks.Changes in neurological function injury score and the percentage of cerebral infarction volume were detected.Transmission electron microscopy was applied to observe the ultrastructure of the blood-brain barrier in rats.The content of Evans blue(EB)staining in the damaged brain tissue was detected.The enzyme-linked immunosorbent assay(ELISA)was applied to detect the levels of interleukin(IL)-1β and IL-18 in damaged brain tissue.Western blot was applied to detect the protein expressions of zonula occludens-1(ZO-1),occludin,TXNIP,Cleaved caspase-1,and NLRP3 in rat brain tissue.Results Compared with those in the sham operation group,rats in the IS group had endothelial edema,loose endothelial cell connections,a large number of phagocytic vesicles,significantly higher neurological function injury score,percentage of cerebral infarction volume,content of EB staining in brain tissue,IL-1β,IL-18,and protein expressions of TXNIP,Cleaved Caspase-1,and NLRP3,but lower protein expressions of ZO-1 and occludin in brain tissue(P＜0.05).Compared with those of the IS group,rats in the low-dose and high-dose ASI groups showed milder endothelial edema and loose endothelial cell connections,significantly lower number of phagocytic vesicles,neurological function injury score,percentage of cerebral infarction volume,content of EB staining in brain tissue,IL-1β,IL-18,and the protein expressions of TXNIP,Cleaved Caspase-1,and NLRP3 proteins,but higher protein expressions of ZO-1 and occludin in brain tissue(P＜0.05).Transfection of OE-TXNIP weakened the protective effects of high-dose ASI on blood-brain barrier injury and neuroinflammation in IS rats.Conclusion ASI alleviates blood-brain barrier injury and inhibits neuroinflammation in IS rats by inhibiting the TXNIP/NLRP3 pathway.
Keywords：asiaticosideischemic strokeblood brain barrierthioredoxin interacting protein/NOD-like receptor protein 3 pathway
Publication Date：2025-02-28
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：5( 223-227 )