Effect and mechanism of PM2.5 exposure on microglia injury in rats with oxygen-glucose deprivation and recovery
Objective To investigate the impact of PM2.5 exposure on microglia injury in rats(GMI-R1)subjected to oxygen-glucose deprivation and recovery(OGD/R),and to explore the related mechanism based on the thioredoxin-inter-acting protein(TXNIP)/NOD-like receptor family pyrin domain-containing 3(NLRP3)pathway.Methods GMI-R1 cells were cultured and divided into the control group,model group,experimental group,and TXNIP inhibitor group,re-spectively.OGD/R models were established in the model group,experimental group and TXNIP inhibitor group,and cells in the control group were cultured routinely.Cells in the experimental group and TXNIP inhibitor group were exposed to PM2.5(50 µg/mL)for 24 h before modeling.Cells in the TXNIP inhibitor group were pretreated with 10 µmol/L rusco-genin(TXNIP inhibitor)for 30 minutes before PM2.5 exposure.After 24 h reoxygenation,flow cytometry was used to de-tect dead cells,and ELISA was used to detect interleukin(IL)-18 and IL-1β in the culture medium supernatant of each group.Western blotting was used to detect TXNIP,NLRP3,apoptosis-associated speck-like protein(ASC),Caspase-1,and Gasdermin D(GSDMD)in cells of each group,and immunofluorescence was used to detect GSDMD-N.Results The cell death rate and the levels of IL-18 and IL-1β in the culture supernatant of the control group,the model group and the ex-perimental group increased in turn,and the cell death rate and the levels of IL-18 and IL-1β in the culture supernatant of the TXNIP inhibitor group were lower than those of the experimental group(all P<0.01).The expression levels of TXNIP,NLRP3,ASC,Caspase-1 and pyroptosis-related proteins GSDMD and GSDMD-N in the control group,model group and experimental group increased in turn;the expression levels of NLRP3,ASC,Caspase-1 and pyroptosis-related proteins GSDMD and GSDMD-N in the TXNIP inhibitor group were lower than those in the experimental group(all P<0.05).Conclusion PM2.5 exposure can aggravate the injury of GMI-R1 cells and intensify the inflammatory response under OGD/R,and the mechanism may be related to promoting the activation of TXNIP/NLRP3 pathway and pyroptosis.
PM2.5ischemic strokethioredoxin-interacting proteinNOD-like receptor family pyrin domain-con-taining 3pyroptosis
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