Effects of FKBP51 acting on Caspase-3 and rat hippocampal CA1 area neuronal necrosis in cerebral ischemia reperfusion injury / 中国基层医药

ABSTRACT

Objective To explore the effect of FKBP51 acting on Caspase-3 and hippocampal CA1 area neu-ronal necrosis in cerebral ischemia reperfusion injury of rat.Methods SD rats were randomly divided into Sham group,ischemia reperfusion group ( I/R group ) , TE buffer group ( TE group ) , FKBP51 antisense oligonucleotide group (FKBP51 ASODN group) and FKBP51 missense oligonucleotide group (FKBP51 MSODN group).Transient global cerebral ischemia rats models were made by four-vessel method.We used Western blot to detect the expression of FKBP51,the effect of FKBP51 ASODN to FKBP51 expression and Caspase-3 activity;while we used HE staining technique to detect FKBP51 ASODN effect to rat hippocampal CA1 area neuronal necrosis.Results (1) In Sham group and I/R group (0min,15min,30min,1h,3h,6h,1d,3d),FKBP51 expressed,and the difference among the groups was no statistical significance (F=0.64,P>0.05).(2)The expression of FKBP51 in FKBP51 ASODN group was obviously reduced, and the difference was statistically significant compared with Sham group ( t =8.21, P <0.05).(3)The expression of Cleaved-Caspase-3 in Sham group obviously declined than the other groups,the differ-ence between them was statistically significant (F=12.31,P<0.05);The expression of FKBP51 in FKBP51 ASODN group was decreasing compared with FKBP51 MSODN group,and the difference was statistical significance(t=9.71, P<0.05).(4)HE staining showedthe number of Sham group (186.3 ±2.5) hippocampal CA1 pyramidal cells was most.The cells arranged densely,and nucleoli were large and round,the difference was statistically significant com-pared with the other groups (χ2 =81.91,P<0.05);The hippocampal CA1 pyramidal cells of I/R group (15.4 ± 2.6),TE group (18.5 ±2.2) and FKBP51 MSODN group (17.5 ±1.8) were almost completely disappeared,only left a few residual cells,a great quantity of denaturated cells which presented karyopykosis,tinctorialed endochylema, ruptured of membrane and released cell content;the hippocampal CA1 pyramidal cells FKBP51 ASODN group (92.8 ±2.6) survival increased significantly compared with other group,the difference was statistically significant (χ2 =52.36,P<0.05).Conclusion In cerebral ischemia reperfusion injury,FKBP51 can enhance the activation of Caspase-3 (Cleaved-Caspase-3) expression and inhibit the survival of the neurons.