ABSTRACT
Objective Effect of fluoxetine on the expression of angiogenic factors in hippocampus of depressive rats.Methods 32 male SD rats (3 month) of SPF level were randomly divided into fluoxetine group (n=8),fluoxetine ± LY294002 intervention group (n=8),model group (n=8) and control group (n =8).Control group without any treatment was free to eat and water for 5 weeks.The rats in the other groups were modeled by chronic,mild and unpredictable multiphase stress.The fluoxetine group was treated with fluoxetine for 2 weeks after modeling,and the intervention group was given LY294002 intervention,then the fluoxetine treatment for 2 weeks,the model group was free to eat and drink for 2 weeks.At the end of the 5th week,all the rats were decapitated and the hippocampus was removed on the ice bath.Western blot was performed to detect the expression of angiogenic factors.Results Compared with the model group (vascular endothelial growth factor(VEGF) (0.44 ± 0.08),fetal liver kinase 1 (FLK1) (0.37 ± 0.15),protein kinase B1 (AKT1) (0.40±0.10),p-AKT1 (0.53±0.07)),the expression of VEGF (0.98± 0.13),FLK1 (1.09± 0.21),AKT1 (1.05±0.05) and p-AKT1 (1.01±0.13)in hippocampus of fluoxetine group were significantly increased,and the differences were statistically significant (P＜ 0.01).And the expression of VEGT,FLK1,p-AKT1 in fluoxetine group increased compared with those of fluoxetine ± LY294002 intervention group (VEGF (0.55±0.08),FLK1 (0.55±0.14) and p-AKT1 (0.60±0.05)),and the difference were statistically significant (P＜0.01).Conclusion Fluoxetine can increase the expression of VEGF/FLK1 and p-AKT1 proteins in the hippocampus of depressed rats,which in turn may be involved in the regeneration of hippocampal blood vessels.This effect of fluoxetine may be related to the PI3K/AKT signaling pathway.