依达拉奉右莰醇对CRS小鼠焦虑抑郁行为的影响和机制研究OA

Objective:To investigate the effects of edaravone borneol(EDB)on anxiety and depressive behaviors in chronic restraint stress(CRS)mice and its potential mechanisms.Methods:Male C57BL/6 mice were randomly assigned to 4 groups(n=8):Control group,Chronic restraint stress(CRS)group,EDB[CRS+EDB(5 mg/kg)]group,and EDB[CRS+EDB(10 mg/kg)]group.The depression model was induced by restraining the mice for 4 hours daily for 21 consecutive days.Anxiety and depressive behaviors were assessed using the open field test,tail suspension test,and forced swimming test.qPCR was used to de-tect the expression of GSDMD,IL-1β,AKT,p62,Beclin1,and LC3Ⅱ mRNA.Western blot was employed to measure the pro-tein expression of p-AKT,p-AMPK,p62,Beclin1,LC3B,GSDMD,GSDMD-N,Pro-IL-1β,IL-1β,and BDNF.Immunoflu-orescence was used to observe and count the expression of the neuronal-specific nuclear protein(NeuN)in the hippocampus.Re-sults:In the open field test,the total distance travelled,time spent in the center zone,and average speed of movement in CRS mice were significantly lower than those in the Control group(P<0.05),while these parameters were higher in EDB-treated groups compared to the CRS group(P<0.05).In the tail suspension and forced swimming tests,the immobility time in CRS mice was significantly longer than that in the Control group(P<0.05),while it was shorter in EDB-treated groups compared to the CRS group(P<0.05).qPCR results showed that compared to the Control group,the expression of GSDMD,IL-1β,and p62 mRNA increased,while the expression of Beclin1 and LC3Ⅱ mRNA decreased in the CRS group(P<0.05).Compared to the CRS group,the expression of GSDMD,IL-1β,and p62 mRNA decreased,while the expression of Beclin1 and LC3Ⅱ mRNA in-creased in EDB-treated groups(P<0.05).Western blot results indicated that compared to the Control group,the expression of p-AKT,p62,GSDMD,GSDMD-N,Pro-IL-1β,and IL-1β increased,while the expression of p-AMPK,Beclin1,LC3B,and BDNF decreased in the CRS group(P<0.05).Compared to the CRS group,the expression of p-AKT,p62,GSDMD,GSDMD-N,Pro-IL-1β,and IL-1β decreased,while the expression of p-AMPK,Beclin1,LC3B,and BDNF increased in EDB-treated groups(P<0.05).Immunofluorescence results showed that the number of NeuN in the CA1,CA3,and DG regions of the hippocampus was significantly lower in the CRS group than in the Control group(P<0.05),while it was significantly high-er in EDB-treated groups compared to the CRS group(P<0.05).Conclusion:EDB may improve anxiety and depressive behav-iors in CRS-induced mice by regulating autophagy through the AKT/AMPK pathway,inhibiting pyroptosis and inflammatory re-sponses,and reducing neuronal damage.