ABSTRACT
OBJECTIVE To investigate whether gas-trodin(GAS)plays a neuroprotective role by activating PI3K/Akt/BACH1 signaling axis to improve glycolytic func-tion.METHODS HT22 cells were treated with Aβ25-35 for 24 h to establish cell damage model.GAS pretreated HT22 cells for 2 h,and Akt agonist SC79,Akt inhibitor MK2206,PI3K inhibitor LY294002 were added 0.5 h before GAS treatment to detect their protective mecha-nisms.Pharmacodynamic research of GAS in this model were divided into six groups:control group,GAS group(GAS 10 μmol·L-1),model group(Aβ25-35 20 μmol·L-1),model +GAS 2.5,5 and 10 μ mol·L-1 group).Mecha-nism research of GAS in this model was divided into 6 groups:control group,Aβ25-35 20 μmol·L-1 group,Aβ25-35 20 μmol·L-1 + GAS 10 μmol·L-1 group,Aβ25-35 + SC79 group(Aβ25-35 20 μmol·L-1 +SC79 10 μmol·L-1),Aβ25-35+MK2206+GAS group(A β 25-35 20 μ mol·L-1 +MK2206 10 μmol·L-1+GAS 10 μmol·L-1),Aβ25-35+LY294002+GAS group(Aβ25-35 20 μmol·L-1+LY294002 10 μmol·L-1+GAS 10 μmol·L-1).Cell viability was detected by MTT,mor-phological changes of cells were observed by micro-scope,ATP content was detected by chemilumines-cence,and pyruvate(PA)content was detected by colo-rimetry.Western blotting was used to detect the protein levels of transcription factor BACH1,key glycolysis enzyme hexokinase(HK1)and PI3K/Akt signaling path-way related proteins PI3K,p-PI3K,Akt and p-Akt.RESULTS The results showed that compared with the control group,the cell morphology of HT22 cells damaged by Aβ25-35 was damaged,the number of cells decreased,the cell body became smaller,the number of dead cells increased,the cell survival rate,ATP and PA contents decreased significantly,and the protein expressions of p-PI3K,p-Akt,BACH1 and HK1 were significantly down-regulated.GAS treatmentcansignificantlyimprovethemor-phology of HT22 cells damaged by Aβ25-35,increase cell survival rate,ATP and PA contents,and up-regulate the expression of p-PI3K,p-Akt,BACH1 and HK1 proteins.SC79 also significantly increased cell survival rate,ATP content,protein expression of BACH1 and HK1.However,the above ameliorative effect of GAS on HT22 cell dam-age induced by Aβ25-35 was antagonized by LY294002 and MK2206.CONCLUSION GAS exerts a neuroprotec-tive effect on Aβ25-35-induced HT22 cell injury by improv-ing glycolytic function through activating PI3K/Akt/BACH1 signaling axis.